The proteasome is a major enzyme that cleaves proteins for antigen presentation. Cleaved peptides traffic to the cell surface, where they are presented in the context of major histocompatibility complex (MHC) class I. Recognition of these complexes by cytotoxic T lymphocytes is crucial for eliminati
Antigen contact sites in class I major histocompatibility complex-restricted, trinitrophenyl-specific T cell receptors
✍ Scribed by Hans Ulrich Weltzien; Sabine Hebbelmann; Ulrike Pflugfelder; Helga Ruh; Bodo Ortmann; Stefan Martin; Antonio Iglesias
- Publisher
- John Wiley and Sons
- Year
- 1992
- Tongue
- English
- Weight
- 376 KB
- Volume
- 22
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Abstract
Cloned trinitrophenyl (TNP)‐specific cytotoxic T cells (CTL) were obtained from mice transgenic for the β chain of the antigen‐specific receptor (TcR) of a K^b^‐restricted, TNP‐specific CTL clone (BT7.4.1). The transgene‐expressing CTL, specific for TNP/K^b^ were found to select for TcR α chains highly similar to that of the transgene donor clone BT7.4.1. In that way, two clones (II/7 and III/1) were identified whose TcR differed from the BT7.4.1 receptor only in their N~α~‐ and J~α~‐sequences, i.e. within the third complementarity‐determining regions of their α chains (CDR3~α~). Moreover, the TcR of clones II/7 and III/1 had both rearranged the same J~α~ element, thus differing from each other by only two amino acids in their V~α~/J~α~ junctional regions. Functionally, however, clone III/1 exhibited unique cytolytic specificities for synthetic, K^b^‐binding TNP‐peptides as well as for chemically TNP‐modified allogeneic (H‐2^k^) target cells. These findings demonstrate that (a) similar to “conventional” peptide antigens, synthetic hapten‐peptide determinants are contacted by CDR3~α~‐determined amino acids of the TcR and (b) in contrast to current models, CDR~α~ also appears to influence the major histocompatibility complex restriction specificity of a given TcR.
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