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Z. Haskova, T.J. Sproule, D.C. Roopenian, B.R. Ksander; A Tissue-specific Minor Histocompatibility Alloantigen that Triggers Rejection of Corneal Allografts . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3213.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Corneal allografts experience immune privilege and have exceptionally good survival as compared with skin allografts. However, immune privilege is not complete and, when corneal allografts are rejected, minor H alloantigens are an important target of immune effector cells. The H3 locus contains several minor H genes within a relatively large segment of DNA on chromosome 2. Our previous results indicate that corneal allografts from congenic mice disparate in the region surrounding the H3b gene were rejected, but skin allografts were accepted. The simplest interpretation of these data is this H3 region contains a putative minor H gene that is expressed in the cornea, but not the skin. We hypothesize there are cornea-specific immunodominant minor H alloantigens within the H3 locus that are expressed in the cornea, but not the skin and are highly immunogenic, terminate immune privilege, and induce vigorous corneal allograft rejection. Methods and Results: To determine the precise position of the minor H gene involved in corneal allograft rejection, donors and recipients were used from a variety of congenic mouse strains (RO3, RO4, R19, and R25) that are disparate at fewer and fewer regions of the H3 locus surrounding the H3b gene. RO3 donor corneas were rejected by 60% of RO4 recipients and 43% of R19 recipients. RO3 donor skin grafts were rejected by 0% of RO4 recipients and 0% of R19 recipients. R19 expresses a smaller region of the H3 locus. Conclusions: The H3 minor H gene locus contains an immunodominant alloantigen that triggers T cell mediated rejection of corneal allografts. This alloantigen is either not expressed on cells within the skin, or expressed but not immunogenic.
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