The use of soluble synthetic peptide combinatorial libraries to determine antigen recognition of T cells

T cells identify by their T-cell receptor (TCR) short peptides in the conte xt of major histocompatiblity complex (MHC) molecules. The interaction of t he trimolecular complex composed of the TCR and MHC bound peptide was exten sively studied using substitution analogs of the original peptide ligands t o define those residues important for T-cell recognition in the peptide cha in. This approach has led to the observation that T-cell recognition is hig hly flexible and that many different peptides can be recognized by an indiv idual TCR. Others and we have recently introduced synthetic peptide combina torial libraries (SCL) to investigate T-cell recognition. Here we review th e SCL-based approaches and describe our current techniques for mapping TCR motifs for CD4+ T cells. The implications of our findings for the understan ding of T-cell recognition, as well as for future applications to study T-c ell responses in infectious diseases, autoimmune disorders and cancer are d iscussed.