Major histocompatibility complex binding affinity of an antigenic determinant is crucial for the differential secretion of interleukin 4/5 or interferon gamma by T cells.

Abstract

Differential activation of CD4+ T-cell precursors in vivo leads to the development of effectors with unique patterns of lymphokine secretion. To investigate whether the differential pattern of lymphokine secretion is influenced by factors associated with either the display and/or recognition of the ligand, we have used a set of ligands with various class II binding affinities but unchanged T-cell specificity. The ligand that exhibited -10,000-fold higher binding to I-AU considerably increased the frequency of interferon y-producing but not interleukin (IL) 4-or IL-5-secreting cells in vivo. Using an established ligand-specific, CD4+ T-cell clone secreting only IL-4, we also demonstrated that stimulation with the highest affinity ligand resulted in interferon 'y production in vitro. In contrast, ligands that demonstrated relatively lower class II binding induced only IL-4 secretion. These data suggest that the major histocompatibility complex binding affinity of antigenic determinants, leading to differential interactions at the T cell-antigenpresenting cell interface, can be crucial for the differential development of cytokine patterns in T cells.

Biological effect of varying peptide binding affinity to the BoLA-DRB3*2703 allele

“…It has been established for mice and man that while high affinity ligands for MHC class II molecules may induce T helper cells to secrete IFN-γ (Th1 response) [10], low affinity ligands may induce the secretion of IL-4 and IL-5 (Th2 response) [13,19]. In addition to playing different roles in host defense, inappropriate Th1/Th2 responses have also been associated with certain diseases [21].…”

“…It has been established that while high affinity ligands for MHC class II (e.g. HLA DRA*0101) [10] may induce T helper cells to secrete IFN-γ and IL-2 (Th1 response), low affinity ligands can induce IL-4 and IL-5 (Th2 response) [13,19]. It is speculated that high affinity interactions between peptides and MHC molecules can lead to increase in the number of stable MHC-peptide complexes on the surface of the antigen presenting cells, which augment the avidity of MHC-peptide-T-cell receptor (TCR) interactions [13].…”

“…HLA DRA*0101) [10] may induce T helper cells to secrete IFN-γ and IL-2 (Th1 response), low affinity ligands can induce IL-4 and IL-5 (Th2 response) [13,19]. It is speculated that high affinity interactions between peptides and MHC molecules can lead to increase in the number of stable MHC-peptide complexes on the surface of the antigen presenting cells, which augment the avidity of MHC-peptide-T-cell receptor (TCR) interactions [13]. It is plausible that susceptibility to bovine mastitis may be attributed, in part, to inappropriate Th1/Th2 immune responses resulting from differences in BoLA-peptide binding affinity that are governed by allelic variants of BoLA class II genes.…”

Human T‐ and B‐Cell Reactivity to the 16 kDa α‐Crystallin Protein of Mycobacterium tuberculosis

“…The relatively infrequent IL-10 response to peptide p91-110 compared with the frequent IFN-g response (Fig. 3) may also indicate that this peptide drives a predominantly Type 1 response, perhaps as a consequence of its high-affinity binding to a wide range of HLA-DR molecules [10,30].…”

The avidity of allospecific cytotoxic T lymphocytes (CTL) determines their cytokine production profile

“…Some other studies support this view. It has been reported that antigenic peptides that bind well to MHC molecules and/or TCR favour the generation of IFN-g-producing cells, whereas peptides that bind less well do not [30,31]. Additionally, it has been shown that TCR transgenic CD4 þ T cells differentiate into IFN-g-producing T cells only when high antigen doses are used for priming [32].…”