A Novel, Nonclassical MHC Class I Molecule Specific to the Common Chimpanzee1 2

All expressed human MHC class I genes (HLA-A, -B, -C, -E, -F, and -G) have functional orthologues in the MHC of the common chimpanzee (Pan troglodytes). In contrast, a nonclassical MHC class I gene discovered in the chimpanzee is not present in humans or the other African ape species. In exons and more so in introns, this Patr-AL gene is similar to the expressed A locus in the orangutan, Popy-A, suggesting they are orthologous. Patr-AL/Popy-A last shared a common ancestor with the classical MHC-A locus >20 million years ago. Population analysis revealed little Patr-AL polymorphism: just three allotypes differing only at residues 52 and 91. Patr-AL is expressed in PBMC and B cell lines, but at low level compared with classical MHC class I. The Patr-AL polypeptide is unusually basic, but its glycosylation, association with β2-microglobulin, and antigenicity at the cell surface are like other MHC class I. No Patr-AL-mediated inhibition of polyclonal chimpanzee NK cells was detected. The Patr-AL gene is present in 50% of chimpanzee MHC haplotypes, correlating with presence of a 9.8-kb band in Southern blots. The flanking regions of Patr-AL contain repetitive/retroviral elements not flanking other class I genes. In sequenced HLA class I haplotypes, a similar element is present in the A*2901 haplotype but not the A*0201 or A*0301 haplotypes. This element, 6 kb downstream of A*2901, appears to be the relic of a human gene related to Patr-AL. Patr-AL has characteristics of a class I molecule of innate immunity with potential to provide common chimpanzees with responses unavailable to humans.

[1]  D. Middleton,et al.  Characterisation of a novel HLA-A pseudogene, HLA-BEL, with significant sequence identity with a gorilla MHC class I gene. , 1999, Tissue antigens.

[2]  M. Nachman,et al.  Estimate of the mutation rate per nucleotide in humans. , 2000, Genetics.

[3]  H. Orr,et al.  A human major histocompatibility complex class I gene that encodes a protein with a shortened cytoplasmic segment. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[4]  A. Hughes,et al.  Molecular cloning of orangutan and gibbon MHC class I cDNA. The HLA-A and -B loci diverged over 30 million years ago. , 1992, Journal of immunology.

[5]  H. Orr,et al.  Human leukocyte antigen F (HLA-F). An expressed HLA gene composed of a class I coding sequence linked to a novel transcribed repetitive element , 1990, The Journal of experimental medicine.

[6]  D. G. Muir,et al.  Rapid evolution of NK cell receptor systems demonstrated by comparison of chimpanzees and humans. , 2000, Immunity.

[7]  F J Ayala,et al.  Evolutionary origin of human and primate malarias: evidence from the circumsporozoite protein gene. , 1995, Molecular biology and evolution.

[8]  M. Nachman,et al.  Contrasting evolutionary histories of two introns of the duchenne muscular dystrophy gene, Dmd, in humans. , 2000, Genetics.

[9]  P. Parham,et al.  HLA-AR, an inactivated antigen-presenting locus related to HLA-A. Implications for the evolution of the MHC. , 1990, Journal of immunology.

[10]  F. Galibert,et al.  A 356-Kb sequence of the subtelomeric part of the MHC Class I region. , 1999, DNA sequence : the journal of DNA sequencing and mapping.

[11]  Margaret Robertson,et al.  Identification and characterization of the familial adenomatous polyposis coli gene , 1991, Cell.

[12]  H. Orr,et al.  Differential expression of HLA-E, HLA-F, and HLA-G transcripts in human tissue. , 1990, Human immunology.

[13]  A. Hughes,et al.  Chimpanzee MHC class I A locus alleles are related to only one of the six families of human A locus alleles. , 1995, Journal of immunology.

[14]  E. Ciccone,et al.  P58 molecules as putative receptors for major histocompatibility complex (MHC) class I molecules in human natural killer (NK) cells. Anti-p58 antibodies reconstitute lysis of MHC class I-protected cells in NK clones displaying different specificities , 1993, The Journal of experimental medicine.

[15]  A. Arnaiz-Villena,et al.  Evolution of MHC-G in primates: a different kind of molecule for each group of species. , 1999, Journal of reproductive immunology.

[16]  P Parham,et al.  Analysis of a successful immune response against hepatitis C virus. , 1999, Immunity.

[17]  N. Saitou,et al.  The neighbor-joining method: a new method for reconstructing phylogenetic trees. , 1987, Molecular biology and evolution.

[18]  D. Pilbeam,et al.  The descent of hominoids and hominids. , 1984, Scientific American.

[19]  J. Kaufman,et al.  Evolutionary conservation of MHC class I and class II molecules--different yet the same. , 1994, Seminars in immunology.

[20]  D. Watkins,et al.  The MHC-E locus is the most well conserved of all known primate class I histocompatibility genes. , 1998, Journal of immunology.

[21]  P Parham,et al.  Structure, function, and diversity of class I major histocompatibility complex molecules. , 1990, Annual review of biochemistry.

[22]  J. Klein,et al.  Nucleotide sequences of chimpanzee MHC class I alleles: evidence for trans‐species mode of evolution. , 1988, The EMBO journal.

[23]  P. Parham,et al.  The Bw4 public epitope of HLA-B molecules confers reactivity with natural killer cell clones that express NKB1, a putative HLA receptor , 1995, The Journal of experimental medicine.

[24]  Peter Parham,et al.  HLA-A and B polymorphisms predate the divergence of humans and chimpanzees , 1988, Nature.

[25]  A. McMichael,et al.  Functions of nonclassical MHC and non-MHC-encoded class I molecules. , 1999, Current opinion in immunology.

[26]  M. Colonna,et al.  A human killer inhibitory receptor specific for HLA-A1,2. , 1996, Journal of immunology.

[27]  D. Watkins,et al.  Major histocompatibility complex class I diversity in a West African chimpanzee population: implications for HIV research , 2000, Immunogenetics.

[28]  A. Arnaiz-Villena,et al.  Primate Mhc-E and -G alleles , 1997, Immunogenetics.

[29]  G. Ferrara,et al.  HLA-C is the inhibitory ligand that determines dominant resistance to lysis by NK1- and NK2-specific natural killer cells. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Jun Wu,et al.  Association of DAP12 with activating CD94/NKG2C NK cell receptors. , 1998, Immunity.

[31]  Eric O Long,et al.  A Human Histocompatibility Leukocyte Antigen (HLA)-G–specific Receptor Expressed on All Natural Killer Cells , 1999, The Journal of experimental medicine.

[32]  N. Takahata,et al.  Evolution of the primate lineage leading to modern humans: phylogenetic and demographic inferences from DNA sequences. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[33]  J. Felsenstein.  CONFIDENCE LIMITS ON PHYLOGENIES: AN APPROACH USING THE BOOTSTRAP , 1985, Evolution; international journal of organic evolution.

[34]  P Parham,et al.  Human diversity in killer cell inhibitory receptor genes. , 1997, Immunity.

[35]  R. Martin.  Primate origins: plugging the gaps , 1993, Nature.

[36]  E. Brooks,et al.  Generation of allospecific natural killer cells by stimulation across a polymorphism of HLA-C. , 1993, Science.

[37]  P Parham,et al.  Gorilla class I major histocompatibility complex alleles: comparison to human and chimpanzee class I , 1991, The Journal of experimental medicine.

[38]  Jeffrey C. Boyington,et al.  Crystal structure of an NK cell immunoglobulin-like receptor in complex with its class I MHC ligand , 2000, Nature.

[39]  P. Parham,et al.  Comparison of Class I MHC Alleles in Humans and Apes , 1990, Immunological reviews.

[40]  Glenys Thomson,et al.  Common chimpanzees have greater diversity than humans at two of the three highly polymorphic MHC class I genes , 2000, Immunogenetics.

[41]  P. Parham,et al.  Structural heterogeneity in HLA-B70, a high-frequency antigen of black populations. , 1993, Tissue antigens.

[42]  L. Pease,et al.  Structure of the MHC A and B locus promoters in hominoids. Insights on the evolution of the class I MHC multigene family. , 1995, Journal of immunology.

[43]  A. Varki,et al.  A chimpanzee genome project is a biomedical imperative. , 2000, Genome research.

[44]  E Soeda,et al.  Molecular dynamics of MHC genesis unraveled by sequence analysis of the 1,796,938-bp HLA class I region. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[45]  Z. Yang,et al.  Estimation of primate speciation dates using local molecular clocks. , 2000, Molecular biology and evolution.

[46]  E. Adams,et al.  A major histocompatibility complex class I allele shared by two species of chimpanzee , 1998, Immunogenetics.

[47]  S. Pääbo,et al.  Extensive nuclear DNA sequence diversity among chimpanzees. , 1999, Science.

[48]  E. Adams,et al.  Genomic analysis of common chimpanzee major histocompatibility complex class I genes , 2001, Immunogenetics.

[49]  A. Lal,et al.  Phylogenetic relationship among the malaria parasites based on small subunit rRNA gene sequences: monophyletic nature of the human malaria parasite, Plasmodium falciparum. , 1996, Molecular phylogenetics and evolution.

[50]  F. Gao,et al.  Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes , 1999, Nature.

[51]  L. Pease,et al.  Evolution of class I Promoter Sequences: Relationship to Function and Diversity , 1995, Immunological reviews.

[52]  Eric O Long,et al.  Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1–HLA-Cw4 complex , 2001, Nature Immunology.

[53]  P. Parham,et al.  NKB1: a natural killer cell receptor involved in the recognition of polymorphic HLA-B molecules , 1994, The Journal of experimental medicine.

[54]  J. Bell,et al.  Functional characterization of HLA‐F and binding of HLA‐F tetramers to ILT2 and ILT4 receptors , 2000, European journal of immunology.

[55]  G. Chelvanayagam.  A roadmap for HLA-A, HLA-B, and HLA-C peptide binding specificities , 1996, Immunogenetics.

[56]  C. Venditti,et al.  Structure and content of the major histocompatibility complex (MHC) class I regions of the great anthropoid apes. , 1996, Human immunology.

[57]  J. Bell,et al.  HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C , 1998, Nature.

[58]  D. Tautz,et al.  Mitochondrial sequences show diverse evolutionary histories of African hominoids. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[59]  J. J. Moore,et al.  Kin selection, social structure, gene flow, and the evolution of chimpanzees. , 1994, Science.