THE PEPTIDE P2CA IS IMMUNODOMINANT IN ALLORECOGNITION OF L(D) BY BETA-CHAIN VARIABLE REGION V-BETA-8(+) BUT NOT V-BETA-8(-) STRAINS

An explanation for the vigorous allograft rejection that results from the recognition by CD8(+) T cells of allogeneic major histocompatibility complex (MHC) molecules has long eluded immunologists. Recent evidence has demonstrated that alloreactivity involves recognition of both the allogeneic MHC molecule and its associated peptide ligand, suggesting the current theory that the strength of the allogeneic response results From the participation of numerous peptides. However, I report here that a single peptide, p2Ca, is immunodominant in allorecognition of the murine MHC class I molecule H-2L(d). The majority of Ld-alloreactive T-cell clones are specific for L(d)-p2Ca and this immunodominance is not due to peptide cross-reactivity. Generation of L(d)-alloreactive cytotoxic T lymphocytes in a strain tolerant to p2Ca did not affect the peptide immunodominance, demonstrating that tolerance to p2Ca is MHC-restricted. The p2Ca-specific clones express beta chain variable region V beta 8 T-cell receptors, however, L(d)-alloreactive cytotoxic T lymphocytes generated in V beta 8(-) mice are not dominated by recognition of p2Ca, suggesting that the T-cell receptor repertoire is a factor in determining peptide immunodominance.