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Z Haskova, DC Roopenian, BR Ksander; An Immunodominant Minor Histocompatibility Alloantigen That Terminates Immune Privilege and Initates Corneal Graft Rejection . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2960.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:Data from experiments using murine orthotopic corneal allografts indicate the immunogenic rules that govern graft rejection are reversed; minor H alloantigens are more important than Major transplantation alloantigens. In previous studies, we observed that minor H alloantigen specific cytotoxic T cells (CTL) are activated, but do not participate in graft rejection. These data imply that minor H specific CD4 T cells are the primary mediators of rejection. These experiments were performed using undefined minor H alloantigens. In the present series of experiments, we examined the role of T cell subpopulations using the genetically defined H3 minor H gene loci. Methods:The H3 loci contains two genes: H3a and H3b. The H3a gene encodes for a peptide sequence that is presented by Class I and recognized by specific CTL. There are no epitopes that activate CD4 T cells. The H3b gene encodes for a peptide sequence that is presented by Class II and recognized by CD4 T cells. There are no epitopes that activate CD8 T cells. Results:Congenic mice were used for either skin, or corneal transplants that displayed the following disparities: (i) H3a + H3b, (ii) H3b only, or (iii) H3a only. Mice rejected either H3a+H3b disparate skin, or corneal allografts at similar rates (70%, and 75% respectively). By contrast, mice rejected H3b disparate corneal allografts vigorously (60% rejected), while H3b disparate skin grafts were not rejected. These grafts are only recognized by CD4 T cells. Corneal allografts that displayed only H3a (recognized by CD8 T cells) were rejected by 30% of recipients. In order to confirm the role of CTL in corneal graft rejection, mice were first immunized with H3a+H3b disparate skin allografts. This activated H3 specific CTL in the presence of helper CD4 T cells. Two weeks after receiving skin grafts, mice were given an H3a only disparate corneal allograft. These grafts can only be rejected by CTL. At seven weeks post grafting 50% of grafts were rejected. Conclusion:(i) Corneal allogafts that display H3b minor H alloantigens do not experience immune privilege as compared with skin grafts, and (ii) minor H specific CTL participate in corneal allograft rejection. These data suggest there may be "immunodominant" minor H alloantigens that are highly immunogenic. When corneal allografts display these minor H alloantigens, immune privilege is terminated and both CTL and DH effector cells mediate graft rejection.
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