Interplay between TCR affinity and necessity of coreceptor ligation: high-affinity peptide-MHC/TCR interaction overcomes lack of CD8 engagement.
CD8 engagement is believed to be a critical event in the activation of naive T cells. In this communication, we address the effects of peptide-MHC (pMHC)/TCR affinity on the necessity of CD8 engagement in T cell activation of primary naive cells. Using two peptides with different measured avidities for the same pMHC-TCR complex, we compared biochemical affinity of pMHC/TCR and the cell surface binding avidity of pMHC/TCR with and without CD8 engagement. We compared early signaling events and later functional activity of naive T cells in the same manner. Although early signaling events are altered, we find that high-affinity pMHC/TCR interactions can overcome the need for CD8 engagement for proliferation and CTL function. An integrated signal over time allows T cell activation with a high-affinity ligand in the absence of CD8 engagement.
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599-7290, USA.
Samantha E
SE
Kerry
Jennifer
J
Buslepp
Lorraine A
LA
Cramer
Robert
R
Maile
Lucinda L
LL
Hensley
Alma I
AI
Nielsen
Paula
P
Kavathas
Barbara J
BJ
Vilen
Edward J
EJ
Collins
Jeffrey A
JA
Frelinger
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D001224:Aspartic Acid / Q000235:genetics; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D006023:Glycoproteins / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D064532:Histocompatibility Antigen H-2D; D008024:Ligands; D008213:Lymphocyte Activation / Q000235:genetics; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008239:Lysine / Q000235:genetics; D021962:Membrane Microdomains / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D017434:Protein Structure, Tertiary / Q000235:genetics; D020239:Receptor Cross-Talk / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
D000956:Antigens, Viral; D016827:CD8 Antigens; D016207:Cytokines; D006023:Glycoproteins; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D008024:Ligands; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus; D001224:Aspartic Acid; D008239:Lysine