TAP-independent selection of CD8+ intestinal intraepithelial lymphocytes.
Intestinal intraepithelial lymphocytes (IEL) are mostly CD8 single positive T cells. IEL with a TCR-alpha(beta) that are CD8 single positive are absent from beta(2)-microglobulin (beta(2)m)-deficient mice, consistent with the idea that these IEL, like other TCR-alpha(beta)+, CD8+ T cells, require class I molecules for positive selection. In contrast, here we show that substantial numbers of TCR-alpha(beta)+, CD8 single positive IEL are present in mice deficient for the transporter associated with Ag processing 1 (TAP 1) gene, although T cells with this phenotype are absent from thymus, spleen, and lymph nodes of these same mice. The majority of TCR-alpha(beta)+, CD8 single positive IEL in TAP-deficient mice expresses CD8 molecules composed of alpha(alpha) homodimers and they express a diverse set of V(beta) gene segments. In addition, the number of TCR-alpha(beta)+, CD4/CD8 double positive IEL is decreased in beta(2)m-deficient mice but not in TAP-deficient mice. The dependence of the two TCR-alpha(beta)+ IEL populations that express CD8alpha(alpha) homodimers on beta(2)m as opposed to TAP molecules is striking. It suggests that TAP-independent but beta(2)m-requiring nonclassical class I molecules expressed by cells in the intestine, such as the thymus leukemia Ag and CD1, could play a pivotal role in the development and/or the accumulation of major subpopulations of TCR-alpha(beta)+ IEL.
Sydora
B C
BC
Department of Microbiology and Immunology and the Molecular Biology Institute, University of California at Los Angeles, CA 90095, USA.
Brossay
L
L
Hagenbaugh
A
A
Kronenberg
M
M
Cheroutre
H
H
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004847:Epithelial Cells; D004848:Epithelium / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015704:CD4 Antigens; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D016693:Receptors, Antigen, T-Cell, alpha-beta; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D001613:beta 2-Microglobulin