CROSS-REACTIVE TRINITROPHENYLATED PEPTIDES AS ANTIGENS FOR CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX-RESTRICTED T-CELLS AND INDUCERS OF CONTACT SENSITIVITY IN MICE - LIMITED T-CELL RECEPTOR REPERTOIRE

The induction of contact sensitivity in mice by hapten reagents such a s trinitrochlorobenzene (TNCB) involves the activation of class II maj or histocompatibility complex (MHC)-restricted, hapten-specific, CD4() T cells. Reports from different laboratories have indicated that the relevant antigenic epitopes in such reactions might include hapten-co njugated, MHC class II-associated peptides. This study for the first t ime directly demonstrates that hapten-peptides account for the majorit y of determinants recognized by trinitrophenyl (TNP)specific CD4(+) T lymphocytes. The sequences of those TNP carrier peptides do not have t o be related to mouse proteins. Thus, we show that TNP-modified peptid es derived from mouse IgG, pigeon cytochrome c or staphylococcal nucle ase known to bind to I-A(b) or from lambda repressor with specificity to I-A(d) as well as TNP-proteins such as bovine serum albumin, ovalbu min or keyhole limpet hemocyanin all create class II-restricted hapten determinants for a number of TNP-specific T cell clones and hybridoma s. All of these cells were induced with cells modified by trinitrobenz ene sulfonic acid (TNBS). In addition, we present arguments indicating that individual TNP-specific helper T cells may cross-react with diff erent TNP-peptides bound to identical class II molecules. Chemical tre atment of antigen-presenting cells with TNCB or TNBS may thus result i n a limited number of particularly repetitive immunodominant hapten ep itopes. Immunodominant epitopes were also indicated by an overrepresen tation of the TCR elements V beta 2 and V alpha 10 in I-A(b)/TNP-speci fic T cells. Most importantly, however, we demonstrate that TNP attach ed to lysine 97 in the staphylococcal nuclease peptide 93-105 (i.e. a clearly ''non-self'' sequence) is able to prime mice for subsequent el icitation of contact sensitivity by TNCB in the absence of foreign pro tein. We take this to indicate that those TNP-peptide determinants def ined by us as immune-dominant are responsible for the induction of con tact sensitivity to haptens.