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

摘要

AbstractThe induction of contact sensitivity in mice by hapten reagents such as trinitrochlorobenzene (TNCB) involves the activation of class II major 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‐conjugated, MHC class II‐associated peptides. This study for the first time directly demonstrates that hapten‐peptides account for the majority of determinants recognized by trinitrophenyl (TNP)‐specific CD4+T lymphocytes. The sequences of those TNP carrier peptides do not have to be related to mouse proteins. Thus, we show that TNP‐modified peptides derived from mouse IgG, pigeon cytochrome c or staphylococcal nuclease known to bind to I‐Abor from λ represser with specificity to I‐Adas well as TNP‐proteins such as bovine serum albumin, ovalbumin or keyhole limpet hemocyanin all create class II‐restricted hapten determinants for a number of TNP‐specific T cell clones and hybridomas. All of these cells were induced with cells modified by trinitrobenzene sulfonic acid (TNBS). In addition, we present arguments indicating that individual TNP‐specific helper T cells may cross‐react with different TNP‐peptides bound to identical class II molecules. Chemical treatment of antigen‐presenting cells with TNCB or TNBS may thus result in a limited number of particularly repetitive immunodominant hapten epitopes. Immunodominant epitopes were also indicated by an overrepresentation of the TCR elements Vβ2 and Vα10 in I‐Ab/TNP‐specific T cells. Most importantly, however, we demonstrate that TNP attached to lysine 97 in the staphylococcal nuclease peptide 93–105 (i.e.a clearly “non‐self” sequence) is able to prime mice for subsequent elicitation of contact sensitivity by TNCB in the absence of foreign protein. We take this to indicate that those TNP‐peptide determinants defined by us as immuno‐dominant are responsible f