Specific low-affinity recognition of major histocompatibility complex plus peptide by soluble T-cell receptor

Abstract

The T-cell receptor is necessary and sufficient for recognition of peptides presented by major histocompatibility complex molecules. Other adhesion molecules, like CD4 or CD8, play an auxiliary role in antigen recognition by T cells. Here we analyse T-cell receptor (TCR) binding using a soluble rather than a cell-bound receptor molecule. A TCR-immunoglobulin chimaera is constructed with the variable and the first constant regions of both the TCR alpha- and beta-chains linked to the immunoglobulin light-chain constant regions. This soluble TCR is expressed, assembled and secreted as an alpha beta heterodimer by a myeloma cell line transfected with the recombinant genes. Furthermore, the soluble TCR is biologically active: it specifically inhibits antigen-dependent activation of the relevant T-cell clones and thus discriminates between proper and irrelevant peptides presented by major histocompatibility complex molecules.

High frequency of cross-reactive cytotoxic T lymphocytes elicited during the virus-induced polyclonal cytotoxic T lymphocyte response.

“…"Affnity" as it is used here, is a loosely defined term which in the case of the CTL probably includes not only the physical affnity of the TCR for MHC plus peptide (which has been shown to be a very weak interaction) (28), but also the interactions of accessory molecules and their receptors (CD2-LFA 3; CD8-MHC; CDllb-intercellular adhesion molecule (ICAM)-I or C3bi; and LFA-I-ICAM-1 or 2), as has been suggested by Williams et al (29). In contrast with the acute infection, the precursor frequencies of virus-specific CTL in the peritoneal cavity of mice 2 mo after infection correlate closely with the numbers of CD8 + CTL expressing the memory CDllb + phenotype in vivo (data not shown) and are quite high (>1 in 10), indicating that there is no inherent poor efficiency in generating precursors in the LDA and suggest that the LDA culture conditions may be favoring the proliferation of memory cells.…”

Alloantibodies can discriminate class I major histocompatibility complex molecules associated with various endogenous peptides.

“…It is possible that the affinity of antibody binding is too high to demonstrate the type of absolute, all or none, binding and peptide dependence that is characteristic of T-cell receptors. This may be a consequence of the higher binding affinity characteristic of antibodies compared to T-cell receptors (23,24). The fact that the ability of alloantibodies to bind MHC can be affected by bound peptide suggests that it may be possible to derive antibodies with peptide specificity that is equivalent to the specificity ofT cells by appropriate types of immunization and screening.…”

Suitability of various membrane lipophilic probes for the detection of trogocytosis by flow cytometry

“…Trogocytosis has been reported to occur for all lymphocyte types tested so far, and for many other cell types of the haematopoietic lineage (2)(3)(4). Several important physiological and pathological consequences of trogocytosis in the immune system have been suggested or, in some cases demonstrated (1,2,4).…”