Connolly J M
Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110.
Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11482-6. doi: 10.1073/pnas.91.24.11482.
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-2Ld. The majority of Ld-alloreactive T-cell clones are specific for Ld-p2Ca and this immunodominance is not due to peptide cross-reactivity. Generation of Ld-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, Ld-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.
CD8 + T细胞识别同种异体主要组织相容性复合体（MHC）分子所导致的强烈同种异体移植排斥反应，长期以来一直困扰着免疫学家。最近的证据表明，同种异体反应性涉及对同种异体MHC分子及其相关肽配体的识别，这支持了当前的理论，即同种异体反应的强度源于众多肽的参与。然而，我在此报告，单一肽p2Ca在小鼠MHC I类分子H - 2Ld的同种异体识别中具有免疫显性。大多数Ld同种异体反应性T细胞克隆对Ld - p2Ca具有特异性，并且这种免疫显性并非由于肽的交叉反应性。在对p2Ca耐受的品系中产生Ld同种异体反应性细胞毒性T淋巴细胞并不影响肽的免疫显性，这表明对p2Ca的耐受是MHC限制的。p2Ca特异性克隆表达β链可变区Vβ8 T细胞受体，然而，在Vβ8 - 小鼠中产生的Ld同种异体反应性细胞毒性T淋巴细胞并不以对p2Ca的识别为主导，这表明T细胞受体库是决定肽免疫显性的一个因素。
