Multiple T cell antigenic determinants identified within a limited region of the horse cytochromec molecule

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Abstract
The antigen fine specificity of T cell hybridomas recognizing the horse apocytochrome c fragment 1–65, restricted to the I-Ab molecule, was determined to gain some insight into the molecular nature of T cell antigenic peptides. Two major groups of clones specific for distinct subsites, namely residues 1–38 and 39–65, could be identified. Hybridomas recognizing the latter determinant were further tested with different horse cytochrome c peptides and analogues. This analysis revealed the presence of at least two epitopes encompassed by residues 47–53 and 48–53. Furthermore, clones specific for the amino acid sequence 48–53 showed considerable heterogeneity in respect to the antigen concentration required to obtain 50% of the maximal interleukin 2 secretion. Most prominent was the heteroclitic response towards tuna cytochrome c which differs at positions 44, 46 and 47 from the horse cytochrome c molecule in the relevant region. Comparison of the conformation of the sequence 43–46 between the two cytochrome c suggests that this segment, which forms a 310 bend, may be important in maintaining the proper structure of the antigenic determinant. Moreover, the variations up to 180-fold in the concentrations of the cross-reacting cytochrome c and peptides required for stimulation were not always correlated with the maximal interleukin 2 secretion they induced. This indicates that the biological response, that is supposed to be an indication of the affinity of the T cell receptor for its ligand, is not necessarily a function of the antigen concentration.