Nonstimulatory peptides contribute to antigen-induced CD8-T cell receptor interaction at the immunological synapse.
It is unclear if the interaction between CD8 and the T cell receptor (TCR)-CD3 complex is constitutive or antigen induced. Here, fluorescence resonance energy transfer microscopy between fluorescent chimeras of CD3zeta and CD8beta showed that this interaction was induced by antigen recognition in the immunological synapse. Nonstimulatory endogenous or exogenous peptides presented simultaneously with antigenic peptides increased the CD8-TCR interaction. This finding indicates that the interaction between the intracellular regions of a TCR-CD3 complex recognizing its cognate peptide-major histocompatibility complex (MHC) antigen, and CD8 (plus the kinase Lck), is enhanced by a noncognate CD8-MHC interaction. Thus, the interaction of CD8 with a nonstimulatory peptide-MHC complex helps mediate T cell recognition of antigen, improving the coreceptor function of CD8.
Department of Immunology, IMM1, The Scripps Research Institute, La Jolla, California 92037, USA.
Pia P
PP
Yachi
Jeanette
J
Ampudia
Nicholas R J
NR
Gascoigne
Tomasz
T
Zal
D000465:Algorithms; D020816:Amino Acid Motifs; D000941:Antigens / Q000737:chemistry; D001426:Bacterial Proteins / Q000378:metabolism; D017252:CD3 Complex / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005434:Flow Cytometry; D031541:Fluorescence Resonance Energy Transfer; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D006825:Hybridomas; D015151:Immunoblotting; D047468:Immunoprecipitation; D008164:Luminescent Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D013997:Time Factors; D014443:Tyrosine / Q000737:chemistry
D000941:Antigens; D001426:Bacterial Proteins; D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D016827:CD8 Antigens; C485182:Cyan Fluorescent Protein; D008164:Luminescent Proteins; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; C054562:yellow fluorescent protein, Bacteria; D049452:Green Fluorescent Proteins; D014443:Tyrosine