HLA and Infectious Diseases

SUMMARY Following their discovery in the early 1970s, classical human leukocyte antigen (HLA) loci have been the prototypical candidates for genetic susceptibility to infectious disease. Indeed, the original hypothesis for the extreme variability observed at HLA loci (H-2 in mice) was the major selective pressure from infectious diseases. Now that both the human genome and the molecular basis of innate and acquired immunity are understood in greater detail, do the classical HLA loci still stand out as major genes that determine susceptibility to infectious disease? This review looks afresh at the evidence supporting a role for classical HLA loci in susceptibility to infectious disease, examines the limitations of data reported to date, and discusses current advances in methodology and technology that will potentially lead to greater understanding of their role in infectious diseases in the future.

[1]  Sophie Palmer,et al.  Complete MHC haplotype sequencing for common disease gene mapping. , 2004, Genome research.

[2]  A. Allison,et al.  NOTES ON SICKLE‐CELL POLYMOKPHISM , 1954, Annals of human genetics.

[3]  D. Lockwood,et al.  Towards understanding the pathology of erythema nodosum leprosum. , 2008, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[4]  Á. Cruz,et al.  Successful treatment of refractory mucosal leishmaniasis with pentoxifylline plus antimony. , 2001, The American journal of tropical medicine and hygiene.

[5]  Shizuo Akira,et al.  Toll-like receptor ligands synergize through distinct dendritic cell pathways to induce T cell responses: Implications for vaccines , 2008, Proceedings of the National Academy of Sciences.

[6]  R. Vierkant,et al.  Associations between SNPs in toll-like receptors and related intracellular signaling molecules and immune responses to measles vaccine: preliminary results. , 2008, Vaccine.

[7]  J. Goedert,et al.  KIR/HLA Pleiotropism: Protection against Both HIV and Opportunistic Infections , 2006, PLoS pathogens.

[8]  Keith Hoots,et al.  Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS , 2002, Nature Genetics.

[9]  Sue Povey,et al.  Gene map of the extended human MHC , 2004, Nature Reviews Genetics.

[10]  R. Vierkant,et al.  Extinction of the human leukocyte antigen homozygosity effect after two doses of the measles-mumps-rubella vaccine. , 2005, Human immunology.

[11]  S. Gabriel,et al.  Assessing the impact of population stratification on genetic association studies , 2004, Nature Genetics.

[12]  M. Olivier.  A haplotype map of the human genome , 2003, Nature.

[13]  Kevin Marsh,et al.  A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria , 1999, Nature Genetics.

[14]  R. Zinkernagel,et al.  A BIOLOGICAL ROLE FOR THE MAJOR HISTOCOMPATIBILITY ANTIGENS , 1975, The Lancet.

[15]  C. Moore,et al.  Evidence of HIV-1 Adaptation to HLA-Restricted Immune Responses at a Population Level , 2002, Science.

[16]  G. Wang,et al.  Influence of HLA-DRB1 alleles and HBV genotypes on interferon-α therapy for chronic hepatitis B , 2005 .

[17]  P. Kaye,et al.  Adoptive Immunotherapy against Experimental Visceral Leishmaniasis with CD8+ T Cells Requires the Presence of Cognate Antigen , 2006, Infection and Immunity.

[18]  H. Whittle,et al.  Class II cytokine receptor gene cluster is a major locus for hepatitis B persistence. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[19]  S Forbes,et al.  The MHC haplotype project: a resource for HLA-linked association studies. , 2002, Tissue antigens.

[20]  M. Olivier.  A haplotype map of the human genome. , 2003, Nature.

[21]  S. Kaufmann,et al.  MHC class Ia‐restricted T cells partially account for β2‐microglobulin‐dependent resistance to Mycobacterium tuberculosis , 2001, European journal of immunology.

[22]  Amalio Telenti,et al.  Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1 , 2007, Nature Genetics.

[23]  C. Kuiken,et al.  Evidence for human leukocyte antigen heterozygote advantage against hepatitis C virus infection , 2007, Hepatology.

[24]  Amanda J. Wilson,et al.  A search for type 1 diabetes susceptibility genes in families from the United Kingdom , 1998, Nature Genetics.

[25]  A. Allison.  The distribution of the sickle-cell trait in East Africa and elsewhere, and its apparent relationship to the incidence of subtertian malaria. , 1954, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[26]  A. Cheever.  A quantitative post-mortem study of Schistosomiasis mansoni in man. , 1968, The American journal of tropical medicine and hygiene.

[27]  Simon C. Potter,et al.  Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A , 2007, Nature.

[28]  B. Roep.  Diabetes: Missing links , 2007, Nature.

[29]  Pardis C Sabeti,et al.  Searching for signals of evolutionary selection in 168 genes related to immune function , 2006, Human Genetics.

[30]  D. Webster,et al.  A DNA Prime-Modified Vaccinia Virus Ankara Boost Vaccine Encoding Thrombospondin-Related Adhesion Protein but Not Circumsporozoite Protein Partially Protects Healthy Malaria-Naive Adults against Plasmodium falciparum Sporozoite Challenge , 2006, Infection and Immunity.

[31]  N. Malats,et al.  Basic molecular genetics for epidemiologists , 2003, Journal of epidemiology and community health.

[32]  S. Kaufmann,et al.  Protective role of gamma/delta T cells and alpha/beta T cells in tuberculosis. , 1995, European journal of immunology.

[33]  L. Abel,et al.  Genetic control of visceral leishmaniasis in a Sudanese population: candidate gene testing indicates a linkage to the NRAMP1 region , 2003, Genes and Immunity.

[34]  Meenakshi Singh,et al.  Stepwise replication identifies a low-producing lymphotoxin-α allele as a major risk factor for early-onset leprosy , 2007, Nature Genetics.

[35]  J. Delgado,et al.  Aspartic Acid Homozygosity at Codon 57 of HLA-DQ β Is Associated with Susceptibility to Pulmonary Tuberculosis in Cambodia1 , 2006, The Journal of Immunology.

[36]  S. Mallal,et al.  HLA-B*5701 screening for hypersensitivity to abacavir. , 2008, The New England journal of medicine.

[37]  E. Thorsby,et al.  The human major histocompatibility system. , 1974, Transplantation reviews.

[38]  Ofer Levy,et al.  Innate immunity of the newborn: basic mechanisms and clinical correlates , 2007, Nature Reviews Immunology.

[39]  S. Mallal,et al.  Drug hypersensitivity in HIV , 2007, Current opinion in allergy and clinical immunology.

[40]  K. Dellagi,et al.  Association analysis of HLA-class II and class III gene polymorphisms in the susceptibility to mediterranean visceral leishmaniasis. , 2001, Human immunology.

[41]  Vicente Planelles,et al.  Host factors influencing susceptibility to HIV infection and AIDS progression , 2007, Retrovirology.

[42]  J. Goedert,et al.  HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage. , 1999, Science.

[43]  J. Todd,et al.  A genome-wide search for human type 1 diabetes susceptibility genes , 1994, Nature.

[44]  E. N. Miller,et al.  Genome-wide scan for visceral leishmaniasis susceptibility genes in Brazil , 2007, Genes and Immunity.

[45]  J. Flynn,et al.  An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection , 1993, The Journal of experimental medicine.

[46]  R. Quinnell.  Genetics of susceptibility to human helminth infection. , 2003, International journal for parasitology.

[47]  C. Freitag,et al.  Differential genetic determination of immune responsiveness to hepatitis B surface antigen and to hepatitis A virus: a vaccination study in twins , 2002, The Lancet.

[48]  C. Moore,et al.  Killer immunoglobulin-like receptors and HLA act both independently and synergistically to modify HIV disease progression , 2005, Genes and Immunity.

[49]  Gen Tamiya,et al.  Complete sequence and gene map of a human major histocompatibility complex , 1999 .

[50]  Elena S. Babaylova,et al.  Complete sequence and gene map of a human major histocompatibility complex , 1999, Nature.

[51]  K. Bojang,et al.  A Randomised, Double-Blind, Controlled Vaccine Efficacy Trial of DNA/MVA ME-TRAP Against Malaria Infection in Gambian Adults , 2004, PLoS medicine.

[52]  R. Kaslow,et al.  HLA and cytokine gene polymorphisms are independently associated with responses to hepatitis B vaccination , 2004, Hepatology.

[53]  Toshihiro Tanaka.  The International HapMap Project , 2003, Nature.

[54]  L. Tsuneto,et al.  Association between killer-cell immunoglobulin-like receptor genotypes and leprosy in Brazil. , 2008, Tissue antigens.

[55]  D. Kwiatkowski,et al.  Variation in the TNF-α promoter region associated with susceptibility to cerebral malaria , 1994, Nature.

[56]  Andrew J. McMichael,et al.  HLA Leaves Its Footprints on HIV , 2002, Science.

[57]  K. Mossman.  The Wellcome Trust Case Control Consortium, U.K. , 2008 .

[58]  M. Newport,et al.  Influence of genetic and environmental factors on the immunogenicity of Hib vaccine in Gambian twins. , 2006, Vaccine.

[59]  J. Todd.  Genetic analysis of type 1 diabetes using whole genome approaches. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[60]  R. Campbell,et al.  Genetic analysis of multicase families of visceral leishmaniasis in northeastern Brazil: no major role for class II or class III regions of HLA , 2002, Genes and Immunity.

[61]  M. Davenport,et al.  Molecular analysis of HLA class II associations with hepatitis B virus clearance and vaccine nonresponsiveness , 2005, Hepatology.

[62]  A. Hill,et al.  Genetics of infectious diseases. , 2004, Human molecular genetics.

[63]  A. Fischer,et al.  A causative relationship between mutant IFNgR1 alleles and impaired cellular response to IFNgamma in a compound heterozygous child. , 1998, American journal of human genetics.

[64]  Jenefer M Blackwell,et al.  Genetic susceptibility to infectious diseases: big is beautiful, but will bigger be even better? , 2006, The Lancet Infectious Diseases.

[65]  D. Conrad,et al.  A worldwide survey of haplotype variation and linkage disequilibrium in the human genome , 2006, Nature Genetics.

[66]  R. Pitchappan,et al.  A major susceptibility locus for leprosy in India maps to chromosome 10p13 , 2001, Nature Genetics.

[67]  T. Hudson,et al.  Chromosome 6q25 is linked to susceptibility to leprosy in a Vietnamese population , 2003, Nature Genetics.

[68]  L. Kaer,et al.  Relative contributions of distinct MHC class I-dependent cell populations in protection to tuberculosis infection in mice. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[69]  J. Blangero,et al.  Genes on chromosomes 1 and 13 have significant effects on Ascaris infection , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[70]  J. Blackwell,et al.  Influence of H–2 complex on acquired resistance to Leishmania donovani infection in mice , 1980, Nature.

[71]  G. Wang,et al.  Influence of HLA-DRB1 alleles and HBV genotypes on interferon-alpha therapy for chronic hepatitis B. , 2005, World journal of gastroenterology.

[72]  B. Bloom,et al.  Evidence for functional subsets of CD4+ and CD8+ T cells in human disease: lymphokine patterns in leprosy. , 1992, Chemical immunology.

[73]  E. N. Miller,et al.  Y Chromosome Lineage- and Village-Specific Genes on Chromosomes 1p22 and 6q27 Control Visceral Leishmaniasis in Sudan , 2007, PLoS genetics.

[74]  R. Vierkant,et al.  The association of class I HLA alleles and antibody levels after a single dose of measles vaccine. , 2003, Human immunology.

[75]  E. Pugh,et al.  Association between the Tumor Necrosis Factor Locus and the Clinical Outcome of Leishmania chagasi Infection , 2002, Infection and Immunity.

[76]  M. Koziel,et al.  Immune responses during acute and chronic infection with hepatitis C virus. , 2008, Clinical immunology.

[77]  J. Todd,et al.  Multifactorial inheritance in type 1 diabetes. , 1995, Trends in genetics : TIG.

[78]  H. Thomas,et al.  Heterozygote advantage for HLA class-II type in hepatitis B virus infection , 1997, Nature Genetics.

[79]  Huei-Wen Chang Liao,et al.  HLA and response to booster hepatitis B vaccination in anti-HBs-seronegative adolescents who had received primary infantile vaccination. , 2008, Vaccine.

[80]  J. Blackwell.  Leishmania donovani infection in heterozygous and recombinant H-2 haplotype mice , 2004, Immunogenetics.

[81]  J. Todd,et al.  Panning for gold: genome-wide scanning for linkage in type 1 diabetes. , 1996, Human molecular genetics.

[82]  J. Carlson,et al.  HIV evolution in response to HLA-restricted CTL selection pressures: a population-based perspective. , 2008, Microbes and infection.

[83]  D. Webster,et al.  A clinical trial of prime-boost immunisation with the candidate malaria vaccines RTS,S/AS02A and MVA-CS. , 2006, Vaccine.

[84]  H. Murray,et al.  Role of L3T4+ and LyT-2+ cells in experimental visceral leishmaniasis. , 1988, Journal of immunology.

[85]  Robert F. Siliciano,et al.  Maintenance of viral suppression in HIV-1–infected HLA-B*57+ elite suppressors despite CTL escape mutations , 2006, The Journal of experimental medicine.

[86]  D. Weatherall,et al.  Cellular mechanism for the protective effect of haemoglobin S against P. falciparum malaria , 1978, Nature.

[87]  G. Fiume,et al.  The aftermath of the Merck's HIV vaccine trial , 2008, Retrovirology.

[88]  Ridley Ds,et al.  Classification of leprosy according to immunity. A five-group system. , 1966 .

[89]  M. Shokrgozar,et al.  HLA-DRB1, DQA1 and DQB1 alleles and haplotypes frequencies in Iranian healthy adult responders and non-responders to recombinant hepatitis B vaccine. , 2008, Iranian journal of immunology : IJI.

[90]  S. Oka,et al.  Evidence of presentation of multiple HIV-1 cytotoxic T lymphocyte epitopes by HLA-B*3501 molecules that are associated with the accelerated progression of AIDS. , 1997, Journal of immunology.

[91]  S. Mallal,et al.  High sensitivity of human leukocyte antigen-b*5701 as a marker for immunologically confirmed abacavir hypersensitivity in white and black patients. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[92]  D. Watkins.  The hope for an HIV vaccine based on induction of CD8+ T lymphocytes--a review. , 2008, Memorias do Instituto Oswaldo Cruz.

[93]  Simon C. Potter,et al.  Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls , 2007, Nature.

[94]  C. Sabin,et al.  Contribution of human leukocyte antigens to the antibody response to hepatitis B vaccination. , 1997, Tissue antigens.

[95]  J. Trowsdale,et al.  Genetic and functional relationships between MHC and NK receptor genes. , 2001, Immunity.

[96]  Gregory A Poland,et al.  Human leukocyte antigen haplotypes in the genetic control of immune response to measles-mumps-rubella vaccine. , 2006, The Journal of infectious diseases.

[97]  M. Newport,et al.  Predominant influence of environmental determinants on the persistence and avidity maturation of antibody responses to vaccines in infants. , 2006, The Journal of infectious diseases.

[98]  Andrew J. McMichael,et al.  Common West African HLA antigens are associated with protection from severe malaria , 1991, Nature.

[99]  A. Allison,et al.  Protection Afforded by Sickle-cell Trait Against Subtertian Malarial Infection , 1954, British medical journal.

[100]  C. Moore,et al.  Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir , 2002, The Lancet.

[101]  N. Bayley,et al.  Failure , 1890, The Hospital.

[102]  G. Poland,et al.  The genetic basis for measles vaccine failure , 2004, Acta paediatrica (Oslo, Norway : 1992). Supplement.

[103]  S. Mallal,et al.  Predicting and diagnosing abacavir and nevirapine drug hypersensitivity: from bedside to bench and back again. , 2006, Pharmacogenomics.

[104]  D. Monos,et al.  SKDM human leukocyte antigen (HLA) tool: A comprehensive HLA and disease associations analysis software. , 2008, Human immunology.

[105]  S. Kaufmann,et al.  Protective role of γ/δ T cells and α/β T cells in tuberculosis , 1995 .

[106]  Laurent Abel,et al.  Leprosy as a genetic model for susceptibility to common infectious diseases , 2008, Human Genetics.

[107]  M. Newport,et al.  Interferon-gamma-receptor deficiency in an infant with fatal bacille Calmette-Guérin infection. , 1996, The New England journal of medicine.

[108]  Tai-Gyu Kim,et al.  Alteration of the influences of HLA classes I and II alleles on the perinatal hepatitis B virus infection after immunoprophylaxis in Korean children. , 2006, Hepatology research : the official journal of the Japan Society of Hepatology.

[109]  I. Berge,et al.  Human CD8+ T-cell differentiation in response to viruses , 2003, Nature Reviews Immunology.

[110]  M. Levin,et al.  Genetic susceptibility to infectious diseases. , 2003, The Pediatric Infectious Disease Journal.

[111]  D. Hartl,et al.  Identification of three new single nucleotide polymorphisms in the human tumor necrosis factor-alpha gene promoter. , 1998, Tissue antigens.

[112]  R. Locksley,et al.  Helper T-cell subsets in mouse leishmaniasis: induction, expansion and effector function. , 1991, Immunology today.

[113]  J. Blackwell,et al.  Immunomodulation of murine visceral leishmaniasis by administration of monoclonal anti‐Ia antibodies: differential effects of anti‐I‐A vs. anti‐I‐E antibodies , 1987, European journal of immunology.

[114]  J. Heeney,et al.  Origins of HIV and the Evolution of Resistance to AIDS , 2006, Science.

[115]  I. Orme,et al.  Disseminated tuberculosis in interferon gamma gene-disrupted mice , 1993, The Journal of experimental medicine.

[116]  G. Gerken,et al.  HLA-DRB1*1301 and *1302 protect against chronic hepatitis B. , 1997, Journal of hepatology.

[117]  J. Blackwell,et al.  Polymorphism in tumor necrosis factor genes associated with mucocutaneous leishmaniasis , 1995, The Journal of experimental medicine.

[118]  D. Weatherall.  ABC of clinical haematology: The hereditary anaemias , 1997, BMJ.

[119]  F. Calafell,et al.  Basic glossary on genetic epidemiology , 2003, Journal of epidemiology and community health.

[120]  David Heckerman,et al.  Human leukocyte antigen-specific polymorphisms in HIV-1 Gag and their association with viral load in chronic untreated infection , 2008, AIDS.

[121]  C. Sia,et al.  The role of HLA class I gene variation in autoimmune diabetes. , 2005, The review of diabetic studies : RDS.

[122]  D. Ridley,et al.  Classification of leprosy according to immunity. A five-group system. , 1966, International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association.

[123]  J. Goedert,et al.  Genetic acceleration of AIDS progression by a promoter variant of CCR5. , 1998, Science.

[124]  Nagasuma Chandra,et al.  HLA‐A*0201‐restricted Cytotoxic T‐cell Epitopes in Three PE/PPE Family Proteins of Mycobacterium tuberculosis , 2008, Scandinavian journal of immunology.

[125]  K. Überla.  HIV Vaccine Development in the Aftermath of the STEP Study: Re-Focus on Occult HIV Infection? , 2008, PLoS Pathogens.

[126]  R. Vierkant,et al.  Associations between human leukocyte antigen (HLA) alleles and very high levels of measles antibody following vaccination. , 2003, Vaccine.

[127]  R. Gie,et al.  Genetic susceptibility to tuberculosis in Africans: a genome-wide scan. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[128]  M. Newport,et al.  A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection. , 1996, The New England journal of medicine.

[129]  A. Cutrell,et al.  Updated clinical risk factor analysis of suspected hypersensitivity reactions to abacavir , 2004, The Annals of pharmacotherapy.

[130]  D. Kwiatkowski,et al.  Tumor necrosis factor SNP haplotypes are associated with iron deficiency anemia in West African children. , 2008, Blood.

[131]  C. Kleeberger,et al.  CCR5 promoter polymorphism and HIV-1 disease progression , 1998, The Lancet.

[132]  T. Hudson,et al.  Susceptibility to leprosy is associated with PARK2 and PACRG , 2004, Nature.

[133]  P. Donnelly,et al.  The effects of human population structure on large genetic association studies , 2004, Nature Genetics.

[134]  Winston A Hide,et al.  Transmission of HIV-1 CTL Escape Variants Provides HLA-Mismatched Recipients with a Survival Advantage , 2008, PLoS pathogens.

[135]  T. Kimman,et al.  Genetic Variation in the Response to Vaccination , 2007, Public Health Genomics.

[136]  J. Bell,et al.  Variation in MICA and MICB genes and enhanced susceptibility to paucibacillary leprosy in South India. , 2006, Human molecular genetics.

[137]  Bin Wang,et al.  Human leukocyte antigen class II DQB1*0301, DRB1*1101 alleles and spontaneous clearance of hepatitis C virus infection: a meta-analysis. , 2005, World journal of gastroenterology.

[138]  J. Hou,et al.  [Association of immune response to hepatitis B vaccine with HLA-DRB1*02, 07, 09 genes in the population of Han nationality in Guangdong Province]. , 2002, Di 1 jun yi da xue xue bao = Academic journal of the first medical college of PLA.

[139]  M. Newport,et al.  Genetic regulation of immune responses to vaccines in early life , 2004, Genes and Immunity.

[140]  D. Watkins,et al.  Rapid and slow progressors differ by a single MHC class I haplotype in a family of MHC-defined rhesus macaques infected with SIV. , 1999, Immunology letters.

[141]  Pardis C Sabeti,et al.  Detecting recent positive selection in the human genome from haplotype structure , 2002, Nature.

[142]  Sophie Palmer,et al.  Genetic Analysis of Completely Sequenced Disease-Associated MHC Haplotypes Identifies Shuffling of Segments in Recent Human History , 2006, PLoS genetics.

[143]  P. Tangkijvanich,et al.  Association of HLA‐DRB1*13 and TNF‐α gene polymorphisms with clearance of chronic hepatitis B infection and risk of hepatocellular carcinoma in Thai population , 2007, Journal of viral hepatitis.

[144]  J. Blackwell,et al.  Differential production of Th1- and Th2-derived cytokines does not determine the genetically controlled or vaccine-induced rate of cure in murine visceral leishmaniasis. , 1991, Journal of immunology.

[145]  K. Uberla.  HIV vaccine development in the aftermath of the STEP study: re-focus on occult HIV infection? , 2008, PLoS pathogens.

[146]  John Trowsdale,et al.  Features of MHC and NK gene clusters. , 2005, Transplant immunology.

[147]  P. Klenerman,et al.  HIV/AIDS. HLA leaves its footprints on HIV. , 2002, Science.

[148]  S. Ahn,et al.  Association between hepatitis B virus infection and HLA‐DR type in Korea , 2000, Hepatology.

[149]  S. Tishkoff,et al.  Global Patterns of Linkage Disequilibrium at the CD4 Locus and Modern Human Origins , 1996, Science.

[150]  H. Dockrell,et al.  Induction of Th1 cytokine responses by mycobacterial antigens in leprosy , 1996, Infection and immunity.

[151]  L. K. Ely,et al.  Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition , 2009, The Journal of experimental medicine.

[152]  C. Taylor,et al.  T lymphocyte subsets in the skin lesions of patients with leprosy. , 1983, Journal of the American Academy of Dermatology.

[153]  R. Zinkernagel,et al.  Speculations on the role of major transplantation antigens in cell-mediated immunity against intracellular parasites. , 1978, Current topics in microbiology and immunology.

[154]  F. Hecht,et al.  Synergy or Independence? Deciphering the Interaction of HLA Class I and NK Cell KIR Alleles in Early HIV-1 Disease Progression , 2007, PLoS pathogens.

[155]  C. Sia,et al.  Genetic susceptibility to type 1 diabetes in the intracellular pathway of antigen processing - a subject review and cross-study comparison. , 2005, The review of diabetic studies : RDS.

[156]  J. Convit,et al.  Serum levels of tumor necrosis factor in patients with American cutaneous leishmaniasis. , 1993, Biological Research.

[157]  S. Kaufmann,et al.  Immune response to Mycobacterium bovis bacille Calmette Guérin infection in major histocompatibility complex class I‐ and II‐deficient knock‐out mice: contribution of CD4 and CD8 T cells to acquired resistance , 1995, European journal of immunology.

[158]  Pardis C Sabeti,et al.  A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC , 2006, Nature Genetics.

[159]  Erik Thorsbv.  The Human Major Histocompatibility System , 1974 .

[160]  Philippe Froguel,et al.  Genomewide association study of an AIDS-nonprogression cohort emphasizes the role played by HLA genes (ANRS Genomewide Association Study 02). , 2009, The Journal of infectious diseases.

[161]  M. Plebanski,et al.  DNA-based vaccines for malaria: a heterologous prime-boost immunisation strategy. , 2000, Developments in biologicals.

[162]  R. Vierkant,et al.  Associations between human leukocyte antigen homozygosity and antibody levels to measles vaccine. , 2002, The Journal of infectious diseases.

[163]  Todd M. Allen,et al.  Design, Expression, and Processing of Epitomized Hepatitis C Virus-Encoded CTL Epitopes1 , 2008, The Journal of Immunology.

[164]  J. Blackwell,et al.  Altered course of visceral leishmaniasis in mice expressing transgenic I‐E molecules , 1992, European journal of immunology.

[165]  E. Shin,et al.  Human leukocyte antigen alleles and haplotypes associated with chronicity of hepatitis B virus infection in Koreans. , 2007, Archives of pathology & laboratory medicine.

[166]  Jacques Fellay,et al.  A Whole-Genome Association Study of Major Determinants for Host Control of HIV-1 , 2007, Science.

[167]  V. Ramesh,et al.  Cytokine profile of circulating T cells of leprosy patients reflects both indiscriminate and polarized T-helper subsets: T-helper phenotype is stable and uninfluenced by related antigens of Mycobacterium leprae. , 1995, Immunology.

[168]  rashmi singh,et al.  A comparative review of HLA associations with hepatitis B and C viral infections across global populations. , 2007, World journal of gastroenterology.

[169]  J. Weissenbach,et al.  Genetic localization of a locus controlling the intensity of infection by Schistosoma mansoni on chromosome 5q31–q33 , 1996, Nature Genetics.

[170]  Steven M. Wolinsky,et al.  Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T lymphocytes , 2002, Nature.

[171]  C. Taylor,et al.  In situ characterization of T lymphocyte subsets in the reactional states of leprosy. , 1983, Clinical and experimental immunology.

[172]  V. Pankratz,et al.  Twin studies of immunogenicity--determining the genetic contribution to vaccine failure. , 2001, Vaccine.

[173]  F. Calafell,et al.  Advanced glossary on genetic epidemiology , 2003, Journal of epidemiology and community health.

[174]  James G. R. Gilbert,et al.  Variation analysis and gene annotation of eight MHC haplotypes: The MHC Haplotype Project , 2008, Immunogenetics.

[175]  T. Beaty,et al.  Genetic predisposition to self-curing infection with the protozoan Leishmania chagasi: a genomewide scan. , 2007, The Journal of infectious diseases.

[176]  D. Kwiatkowski,et al.  Tumor necrosis factor promoter polymorphism and susceptibility to lepromatous leprosy. , 1997, The Journal of infectious diseases.

[177]  A. Hill,et al.  Reverse immunogenetics: from HLA-disease associations to vaccine candidates. , 1996, Molecular medicine today.

[178]  A. Lemainque,et al.  A major susceptibility locus on chromosome 22q12 plays a critical role in the control of kala-azar. , 2003, American journal of human genetics.

[179]  T. Ide,et al.  Phase I clinical study of a personalized peptide vaccination for patients infected with hepatitis C virus (HCV) 1b who failed to respond to interferon-based therapy. , 2007, Vaccine.

[180]  Clive E. Bowman,et al.  Genetic variations in HLA-B region and hypersensitivity reactions to abacavir , 2002, The Lancet.

[181]  A. Hill,et al.  Identification of conserved antigenic components for a cytotoxic T lymphocyte-inducing vaccine against malaria , 1995, The Lancet.

[182]  E. Yunis,et al.  The immune response to hepatitis B vaccine in humans: inheritance patterns in families , 1992, The Journal of experimental medicine.

[183]  E. N. Miller,et al.  Genome-wide scans for leprosy and tuberculosis susceptibility genes in Brazilians , 2004, Genes and Immunity.

[184]  Paul R Burton,et al.  Key concepts in genetic epidemiology , 2005, The Lancet.