Role of TCR-restricting MHC density and thymic environment on selection and survival of cells expressing low-affinity T cell receptors.
H-Y-specific T cell receptor (TCR) transgenic mice express an MHC class I H-2D(b)-restricted TCR specific for a male antigen-derived peptide (H-Y). Selection and survival of cells expressing this low-affinity TCR were analyzed under optimal and sub-optimal conditions. Optimal conditions were provided by a thymic environment with high H-2D(b) density. Sub-optimal conditions were provided by a thymic environment with decreased H-2D(b) density or by an athymic environment with either high or low H-2D(b) density. Whereas negative selection was still guaranteed under sub-optimal conditions, selection and survival efficiency of cells expressing the transgenic TCR were strongly dependent on optimal conditions. These results indicated that both a thymic microenvironment and a high density of TCR-restricting MHC molecules were needed to ensure selection and maintenance of cells expressing TCR with low affinity and hence a more diverse T cell repertoire.
Martinic
Marianne M
MM
Institute of Experimental Immunology, Department of Pathology, University Hospital Zurich, Zurich, Switzerland. marianne.martinic@joslin.harvard.edu
Rocha
Benedita
B
McCoy
Kathy D
KD
Hengartner
Hans
H
Zinkernagel
Rolf M
RM
D000818:Animals; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D006182:H-Y Antigen / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D017634:Self Tolerance; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D006183:H-2 Antigens; D006182:H-Y Antigen; D064532:Histocompatibility Antigen H-2D; D011948:Receptors, Antigen, T-Cell