Peptide analogs with different affinities for MHC alter the cytokine profile of T helper cells

The interaction of the TCR with the immunogenic peptide bound to MHC class II molecules leads to the activation of CD4(+) T helper cells, T helper cells have been divided into two subsets, T(h)1 and T(h)2, on the basis of the cytokines secreted by them, T(h)1 cells which secrete IL-2, IFN-gamma and tumor necrosis factor-beta induce delayed-type hypersensitivity, while T(h)2 cells secreting IL-4, IL-5, IL-6 and IL-10 induce humoral immune response, However, the mechanism of selective activation of T(h)1 and T(h)2 cells in response to different antigens is not fully understood, In this study we examined the selective activation of T(h)1 and T(h)2 cells in response to strongly immunogenic synthetic peptides EYK(EYA)(3), abbreviated as K3; EYK(EYA)(4), abbreviated as K4; and EYKEYAAYA(EYA)(2), abbreviated as K1A2, These peptides are recognized by H-2(d) T cells in the context of I-A(d), and are strongly cross-reactive in both T cell response and antibody response, The peptide K1A2 has very high affinity for I-A(d) while K3 has a much lower affinity, K4 has affinity intermediate between K1A2 and K3, The peptide K1A2 induced T(h)1 and K3 induced T(h)2 cells in BALB/c mice as suggested by their cytokine profiles, K4 induced both T(h)1- and T(h)2-type cytokines. This was also confirmed by the analysis of peptide-specific antibody responses. K3 induced primarily IgG1 response, whereas K4 induced both IgG1 and IgG2a responses in vivo, There was a shift toward a T(h)1-type cytokine profile when K3-primed T cells were challenged with K1A2 in vitro but K1A2-primed cells did not show any shift when challenged with K3, Immunization with higher doses of K3 shifted the response towards T(h)1 type, while immunization with lower doses of K1A2 did not shift the response toward T(h)2. We conclude that cells primed with high-affinity peptide are committed to differentiate into T(h)1 irrespective of the priming dose and affinity of challenge antigen, On the other hand, the differentiation of cells primed with low-affinity peptide depends upon the dose of immunization and binding affinity of the challenge antigen for MHC.