A role for the region encompassing the c" strand of a TCR V alpha domain in T cell activation events.
The distinct strand topology of TCR V alpha domains results in a flatter surface in the region encompassing the c" strand than the corresponding region in Ig V domains. In the current study a possible role for this region in T cell activation has been investigated by inserting a potential glycosylation site at V alpha residue 82. This residue is in proximity to the c" strand and distal to the putative interaction site for cognate peptide:MHC ligand. An additional N-linked carbohydrate at this position would create a protrusion on the V alpha domain surface, and this may interfere with TCR aggregation and/or recruitment of signaling molecules. The modified TCR has been expressed in transfected T cells, and the phenotype following stimulation has been compared with that of cells expressing the wild-type TCR. The mutation has significant effects on activation-induced cell death and TCR internalization, but, unexpectedly, does not affect IL-2 secretion. Furthermore, analyses with tetrameric, peptide:MHC class II complexes suggest that the mutation decreases the ability of the TCR to aggregate into a configuration compatible with avid binding by these multivalent ligands.
Qadri
A
A
Center for Immunology and Cancer Immunobiology Center, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
Radu
C G
CG
Thatte
J
J
Cianga
P
P
Ober
B T
BT
Ober
R J
RJ
Ward
E S
ES
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D015151:Immunoblotting; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D004676:Myelin Basic Protein / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D019000:Phosphotyrosine / Q000276:immunology; D017434:Protein Structure, Tertiary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D014162:Transfection / Q000276:immunology
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; C405722:myelin basic protein 1-11; D019000:Phosphotyrosine