The specificity of cellular immune responses in guinea pigs. I. T cells specific for 2,4-dinitrophenyl-o-tyrosyl residues.

Abstract

Responses of thymus-derived (T) lymphocytes to hapten-protein conjugates are very largely specific for carrier-and conjugate-specific determinants ; such responses rarely show the hapten specificity which predominates in the responses of thymus-independent bone marrow-derived (B) lymphocytes to similar antigens (1) . These findings, and similar observations in other antigen systems, have led to the suggestion that T and B cells have distinctive libraries of specific receptors, or perhaps very different requirements for activation (2-4) . However, it has not in fact been possible to precisely analyze T-cell receptor specificity, except in a few cases, because simple, well defined chemical determinants can rarely be employed for this purpose . Nevertheless, T-cell responses apparently specific for hapten occur under certain circumstances, as described by Leskowitz et al . (5) in the p-azo-benzenearsonate system, and in recent extensions of these studies by Alkan et al . (6) . In addition, Benacerraf and Gell (7) reported that immunization of guinea pigs with 2,4,6-trinitrophenylated Mycobacteria induced a state of delayed hypersensitivity (DH)' which could be elicited by 2,4,6-trinitrophenyl (TNP) coupled to several proteins, and these results have recently been confirmed by Trefts et al .' In the present experiments, the specificity of T lymphocytes has been explored by immunizing inbred guinea pigs to 2,4-dinitrophenyl (DNP) Mycobacteria . We confirm that DH responses to a variety of DNP proteins can be obtained in such animals .and in addition we show that contact reactivity to 1-fluoro-2,4-dinitrobenzene (DNFB) and in vitro DNA-synthetic and migration inhibition responses are obtained . However, several lines of evidence clearly demonstrate *Present address :

Cell-mediated lympholysis to H-2-matched target cells modified with a series of nitrophenyl compounds.

“…These findings include the observations that: (a) H-2 homology is required between stimulator and target cells (10,11,13); (b) TNP-modified and NIP-AGG-modified stimulating cells generate clones of effectors which can distinguish between these two modifying agents (11); (c) cold target inhibition can occur only when the competing, nonradioactive target cells are both H-2-matched and modified with the same agent as the stimulating cells (11,13); and (d) inhibition of the lysis of modified target cells is obtained by anti-H-2 sera directed against the modified targets (16). Furthermore, the observations presented in this report are compatible with the results of Janeway and co-workers using related nitrophenyl compounds (3,4) in which specificity was shown to include both the nitrophenyl groups and part of the protein carrier.…”

Hapten-reactive inducer T cells. I. Definition of two classes of hapten-specific inducer cells.

“…In contrast, hapten-specific inducer cells are extremely rare. The data presented have, as well as studies by others (43)(44)(45), demonstrate that the vast majority of inducer-cell clones recognize hapten in association with a defined sequence of amino acids. The major consequence of this conjugate-specific recognition is a highly stringent requirement for stimulation: inducer cells can be stimulated only by a restricted set of proteins that carry the precise amino acid sequence of the original immunogen.…”

Hypothesis: The MHC-restricted T-cell receptor as a structure with two multistate allosteric combining sites

“…In these studies, it was found that a change of one or two residues in the amino acid sequence of either A or MHC caused a loss of recognition (Keck, 1975;Zinkernagel, 1976;Maizels et al, 1980;Whitmore and Gooding, 1981;DeWaal et al, 1983;Townsend et al, 1983a, b;Berkower et al, 1984;Lin et al, 1984). Other studies have indicated that hapten-specific T-cells' are also capable of recognizing subtle differences in hapten structures (Gell and Silverstein, 1962;Silverstein ?nd Gell, 1962;Janeway et al, 1975Janeway et al, , 1976aLevy and Shearer, 1982;Rao et al, 1984).…”