An immunodominant minor histocompatibility alloantigen that initiates corneal allograft rejection1

Background. Murine orthotopic corneal allografts experience immune privilege and have good survival as compared with skin allografts. However, privilege is not complete, and some grafts are still rejected. Unexpectedly, corneas expressing minor histocompatibility (H) alloantigens are rejected at a higher rate than major histocompatibility complex (MHC) disparate grafts. We hypothesize that certain immunodominant minor H alloantigens are extremely immunogenic when expressed in corneal tissue, terminate ocular immune privilege, and initiate corneal allograft rejection. Methods and Results. Corneal allograft survival and the role of CD4+ T cells and CD8+ T cells were examined in corneal transplants that expressed genetically defined minor H3 alloantigens. The H3 locus contains at least two minor H genes. H3a is presented by MHC class I and recognized exclusively by CD8+ T cells. H3b is presented by class II and recognized exclusively by CD4+ T cells. Congenic strains that differ from C57BL/10 at (1) H3a, (2) H3b, or (3) H3a+H3b were used for orthotopic corneal and skin transplants. Donor corneas expressing either H3a or H3a+H3b experienced immune privilege and survived longer than skin allografts. By contrast, donor corneas expressing H3b (recognized by CD4+ T cells) experienced vigorous rejection and were eliminated faster than skin allografts. Conclusion. There are minor H alloantigens that terminate ocular immune privilege and initiate corneal allograft rejection. These minor H alloantigens are more immunogenic when expressed in corneal tissue than when they are expressed in skin allografts.

[1]  B. Seitz,et al.  Risk factors for corneal allograft rejection: intermediate results of a prospective normal-risk keratoplasty study , 2002, Graefe's Archive for Clinical and Experimental Ophthalmology.

[2]  U. Pleyer,et al.  Corneal Allograft Rejection: Current Understanding , 2002, Ophthalmologica.

[3]  J. Niederkorn.  Immune privilege in the anterior chamber of the eye. , 2002, Critical reviews in immunology.

[4]  B. Ksander,et al.  Cytotoxic T cells play no essential role in acute rejection of orthotopic corneal allografts in mice. , 2001, Investigative ophthalmology & visual science.

[5]  Kenji Inoue,et al.  Histocompatibility Y antigen compatibility and allograft rejection in corneal transplantation , 2000, Eye.

[6]  J. Pepose,et al.  CD4+ T cells are critical for corneal, but not skin, allograft rejection. , 2000, Transplantation.

[7]  B. Ksander,et al.  Detection of minor alloantigen-specific cytotoxic T cells after rejection of murine orthotopic corneal allografts: evidence that graft antigens are recognized exclusively via the "indirect pathway". , 1999, Transplantation.

[8]  J. Streilein,et al.  Role of CD4+ T cells in immunobiology of orthotopic corneal transplants in mice. , 1999, Investigative ophthalmology & visual science.

[9]  J. Niederkorn.  The immune privilege of corneal allografts. , 1999, Transplantation.

[10]  N. Shastri,et al.  Positional cloning and molecular characterization of an immunodominant cytotoxic determinant of the mouse H3 minor histocompatibility complex. , 1998, Immunity.

[11]  Z. Haskova,et al.  [The significance of gender incompatibility in donors and recipients and the role of minor histocompatibility antigens in corneal transplantation]. , 1997, Ceska a slovenska oftalmologie : casopis Ceske oftalmologicke spolecnosti a Slovenske oftalmologicke spolecnosti.

[12]  B. Ksander,et al.  Murine orthotopic corneal transplantation in high-risk eyes. Rejection is dictated primarily by weak rather than strong alloantigens. , 1997, Investigative ophthalmology & visual science.

[13]  B. Ksander,et al.  Immune deviation in relation to ocular immune privilege. , 1997, Journal of immunology.

[14]  Z. Haskova,et al.  The role of major and minor histocompatibility antigens in orthotopic corneal transplantation in mice. , 1996, Folia biologica.

[15]  J. Pepose,et al.  T-cell mediated responses in a murine model of orthotopic corneal transplantation. , 1995, Investigative ophthalmology & visual science.

[16]  D. Easty,et al.  Non-MHC antigens and their relative resistance to immunosuppression after corneal transplantation , 1995, Eye.

[17]  D. Roopenian,et al.  The functional basis of minor histocompatibility loci. , 1993, Journal of immunology.

[18]  J. Streilein,et al.  ORTHOTOPIC CORNEAL TRANSPLANTATION IN MICE—EVIDENCE THAT THE IMMUNOGENETIC RULES OF REJECTION DO NOT APPLY , 1992, Transplantation.

[19]  D. Easty,et al.  Effect of mismatches for major histocompatibility complex and minor antigens on corneal graft rejection. , 1991, Investigative ophthalmology & visual science.

[20]  J. Niederkorn,et al.  ACCEPTANCE OF H‐Y‐DISPARATE CORNEAL GRAFTS DESPITE CONCOMITANT IMMUNIZATION OF THE RECIPIENT , 1991, Transplantation.

[21]  S. Tuft,et al.  The corneal endothelium , 1990, Eye.

[22]  D. Bailey,et al.  A rapid method of grafting skin on tails of mice. , 1960, Transplantation bulletin.