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.
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 approximately 10,000-fold higher binding to I-Au considerably increased the frequency of interferon gamma-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 gamma 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-antigen-presenting cell interface, can be crucial for the differential development of cytokine patterns in T cells.
Kumar
V
V
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024-1489, USA.
Bhardwaj
V
V
Soares
L
L
Alexander
J
J
Sette
A
A
Sercarz
E
E
D000595:Amino Acid Sequence; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000939:Epitopes; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008285:Major Histocompatibility Complex; D051379:Mice; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000378:metabolism* / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D015848:Interleukin-5; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D015847:Interleukin-4; D007371:Interferon-gamma