Interaction of 2C T cells with a hybrid Ld molecule bearing an alpha 3 domain derived from the class IB molecule, Qa-2.
The CD8 co-receptor interacts with nonpolymorphic residues on class I molecules. LQ3, a laboratory engineered Ld molecule bearing an alpha 3 domain derived from Q7 (Qa-2), interacts poorly with anti-Ld CD8-dependent T cells. 2C TCR transgenic mice bear a receptor specific for the p2Ca peptide bound to Ld. The authors show that although this peptide interacts with LQ3, LQ3 APC fail to activate splenic 2C CD8 T cells in vitro in the absence of IL-2, while control Ld APC do. The authors have used this receptor ligand pair to examine negative selection within the thymus of (B6 x C3H.Ld)F1 versus (B6 x C3H.LQ3)F1 radiation chimeras repopulated with 2C bone marrow cells. While positive selection occurs normally in (B6 x C3H)F1 chimeras, animals expressing either Ld or LQ3 fail to generate 2C CD8+ cells. Thus, either CD8 is not required for negative selection of this TCR or a weak interaction of CD8 with LQ3 is sufficient. TSA-1, a developmentally regulated marker, was used to follow the process of negative selection. The results show that deletion of 2C T cells does not occur until thymocytes reach the double positive (DP) stage. Furthermore, the authors noted a small population of DP TSA-1hi cells remains, while DP TSA-1int and TSA-1lo cells are absent. These data support the notion that thymocytes either reach a particular stage of development or locate in an appropriate intrathymic compartment before they undergo negative selection.
Ungchusri
T
T
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235-9048, USA.
Kettman
J R
JR
Forman
J
J
D000818:Animals; D000953:Antigens, Protozoan / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D016827:CD8 Antigens / Q000276:immunology*; D002454:Cell Differentiation; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D016130:Immunophenotyping; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology; D011993:Recombinant Fusion Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology; D014643:Variant Surface Glycoproteins, Trypanosoma
D000953:Antigens, Protozoan; D000954:Antigens, Surface; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D010455:Peptides; C032907:Q surface antigens; D011993:Recombinant Fusion Proteins; D014643:Variant Surface Glycoproteins, Trypanosoma; C070842:trypomastigote specific surface antigen