Similarity Of Specificity In CD8+ T-cell Response To Alloantigen And Nominal Antigen

In conventional T-cell reactivity directed against pathogens, the specificity of T cell allows inspection of peptide bound by host major histocompatibility complex (MHC) on the surface of other cells. However, cross-reactivity seems to be an intrinsic property of the T cell receptor (TCR) required, because a single TCR must possess the ability.to interact with both self-MHC during positive selection and at least one combination of foreign antigenic peptide presented by self-MHC. Both theoretical considerations and experimental evidence suggest that a single TCR must recognize over one million different peptides in the context of a single MHC molecule so that T cells would mount a rapid and efficient immune response against invading pathogens, taking account of the limited number of T cells. So T cells seem to combine high specificity with the ability of cross-reactivity.The allograft rejection enlarges our understanding of T-cell recognition and refers to the ability of T cells to recognize allo-MHC molecules. One hallmark of alloreactivity is the high precursor frequencies of alloreactive T cells, which are 100-fold to 1,000-fold higher than the precursor frequencies of naive T cells specific for any singe self-MHC-restricted peptide determination. This striking difference in precursor frequency allows one to question whether alloreactive and self-restricted T cells interact with pMHC in the same way and whether the alloreactive T cells are equally peptide specific as the self-restricted T cells. In this study, we compare the reactivity of self-restricted vs alloreactive T cells to a single pMHC complex.Previously, we successfully expressed a HLA-A2/IgG1 fusion protein (HLA-A2 dimer) which could be attached to monocytes by the Fc fragment. For HLA-A*0201 monocytes, the epitope provided by the dimer was as the same as the monocytes original holding. Our studies showed here that the autologous monocyte attached by peptide/HLA-A2 dimer is more effective in expanding peptide-specific T cells from HLA-A*0201 PBLs than the autologous monocyte without dimer. The cross-reactivities between laNS3 and 1bNS3 were described in nominal antigen recognition model. For the HLA-A2-ve PBLs, the peptide/HLA-A2 complex provided by the autologous monocyte attached by peptide/HLA-A2 dimer can be recognized as allo-epitope. The responsibility of alloreactive T-cell induced by the peptide/HLA-A2 complex was demonstrated in this model and was compared with the responsibility of self-restricted T-cell induing by the same single epitope.In this study, we found no obvious different of peptide cross-reactivity between self-restricted and alloreactive T cells. Instead, we found that the alloreactive T cells exhibited a high specificity combined with the ability of cross-reactivity just as the self-restricted T cells do, and the degree of peptide cross-reactivity of alloreactive T cells is similar to that of self-restricted T cells. By integrating the apparently conflicting requirements of TCR (specificity and cross-reactivity) in two recognition models, our results indicate that peptide degeneracy is just the similarity between the alloantigen and nominal antigen recognition rather than the difference distinguishing allorecognition from conventional recognition and the T cell recognizing of alloantigen combine peptide specificity and cross-reactivity as recognizing of nominal antigen.