Ksander B. R.

Schepens Eye Research Institute, Harvard Medical School, Boston, MA

Background: Donor minor histocompatibility antigens are one of the main targets of specific T cells during rejection of orthotopic corneal allografts in mice and can be expressed either (i) indirectly by recipient antigen presenting cells, or (ii) directly by MHC molecules on the surface of the donor cornea. During corneal allograft rejection, T cells are activated that are specific for minor H alloantigens presented by either class II (recognized by CD4 T helper cells), or class I (recognized by CD8 cytotoxic T cells). Although these two populations of T cells are activated, only CD4 T helper cells participate in graft rejection. Since minor H specific cytotoxic T cells (CTL) are activated, but do not mediate, graft rejection, we hypothesize that corneal endothelial cells are resistant to lysis by CTL due to a failure to directly present minor H antigens via class I.
Methods: We have used the genetically defined H3 minor H gene loci to study the expression and recognition of minor H antigens on corneal endothelial cells. Our results indicate there are two defects in corneal endothelial cells that make them resistant to CTL: (i) insufficient class I, and (ii) a failure to properly process the H3 minor alloantigen due to an abnormal expression of proteasome subunits.
Conclusion: We predict the ocular environment modulates the expression of proteasomes in corneal endothelial cells and in this manner, alters the repertoire of minor H alloantigens expressed by class I. Altering the class I pathway of antigen processing may be an important mechanism that is responsible for maintaining immune privilege in the eye.

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