On the thymus in the differentiation of "H-2 self-recognition" by T cells: evidence for dual recognition?

Abstract

The dual specificity of thymus-derived lymphocytes (T cells) for structures coded by the major histocompatibility gene complex (MHC) 1 and for foreign antigens (X) appears to be a general finding in mice and is likely to be a more universal phenomenon in higher vertebrates. Thus, all T-cell functions that have been tested in mice i.e., T cells involved in nonlytic helper, delayed type hypersensitivity, and macrophage activation functions are specific for the murine MHC (H-2) coded structure mapping to the I region (1-5), whereas cytotoxic T-cell activity is specific for H-2K or D (6-11). Similarly, cytotoxicity appears to be MHC-restricted in the rat (12), in humans (13), and in chickens (14). This restriction of T cells by MHC determinants contrasts with the apparently complete absence of H-2 restrictedness of B-cell functions or of their antibody products.Although the phenomenology is clear and well accepted, the explanation of it is controversial and therefore many hypotheses and speculations have attempted to catch the elusive nature of the T-cell receptor; because it is generally felt that this dual specificity of T cells reflects and may therefore reveal unique properties of the T-cell receptor(s). Two models of associative T-cell recognition have been proposed: first the dual recognition model (1-9, 14, 15) where T cells recognize two distinct antigenic entities i.e., self-H-2 structures and foreign antigen X with two separate receptors. Second, the single receptor model, which proposes that T cells possess one single receptor specificity that recognizes a neoantigenic determinant (NAD) formed either by a complex of self and

Extensive proliferation of T cell lineage‐restricted progenitors in the thymus: an essential process for clonal expression of diverse T cell receptor β chains

“…Whereas cellular and molecular mechanisms of T cell development at stages after TCR expression have been well clarified [36][37][38][39], relatively little attention had been directed to the earlier stages including lineage commitment. We have previously shown that T cell lineage restriction occurs at a prethymic stage [16-18, 40, 41].…”

Maturational stage-dependent thymocyte responses to TCR engagement

“…Positive selection ensures that T cells respond to foreign antigens in conjunction with self-MHC molecules [1][2][3]. This is achieved by allowing T cells recognizing self peptides presented by self-MHC molecules to mature, resulting in differentiation of CD4 + CD8 + TCR low double-positive (DP) thymocytes into CD4 + CD8 -TCR high or CD4 -CD8 + TCR high singlepositive (SP) T cells [4][5][6].…”

Role of TCR‐restricting MHC density and thymic environment on selection and survival of cells expressing low‐affinity T cell receptors

“…Because continuous interaction between TCR and TCRrestricting MHC molecules is crucial for T cell selection and survival [6][7][8][9][10][11][12] and because it is known that cells expressing high-affinity TCR are much less susceptible to TCR-restricting MHC density [13,14], this study analyzed whether changes in TCR-restricting MHC density had a direct influence on the selection and survival of cells expressing low-affinity TCR. Experiments were therefore performed using the low-affinity [15] MHC class I H-2D b -restricted H-Y-specific transgenic TCR [16] under optimal and sub-optimal conditions.…”