Qa-2-dependent selection of CD8alpha/alpha T cell receptor alpha/beta(+) cells in murine intestinal intraepithelial lymphocytes.
Murine intestinal intraepithelial lymphocytes (iIELs) are made up of a heterogeneous mix of T cells with unique phenotypes. Whereas CD8(+) T cells in peripheral lymphoid organs use CD8alpha/beta and are selected on MHC class Ia molecules, a majority of iIELs use CD8alpha/alpha. Here, we report that the presence of CD8alpha/alpha TCR-alpha/beta cells in iIELs is independent of classical MHC class I molecules K(b) and D(b), as illustrated by their presence in K(b)/D(b) double-knockout mice and in mice lacking a nonclassical MHC class I molecule, CD1d. Most strikingly, their presence is decreased by approximately 70% in mice lacking transporter associated with antigen processing (TAP). The TAP-dependent nonclassical MHC class I molecule Qa-2 is strongly implicated in the presence of these cells, as inferred from the low numbers of CD8alpha/alpha TCR-alpha/beta T cells in mice deficient in Qa-2 genes. Second, a Qa-2-transgenic mouse made in a Qa-2(-) strain showed an increase in the numbers of CD8alpha/alpha cells among its iIELs. Thus, the presence of CD8alpha/alpha TCR-alpha/beta cells in iIELs is mainly dependent on the nonclassical MHC class I molecule Qa-2.
Das
G
G
Section of Immunobiology, Yale University School of Medicine, and the Howard Hughes Medical Institute, New Haven, Connecticut 06520-8011, USA.
Gould
D S
DS
Augustine
M M
MM
Fragoso
G
G
Sciutto
E
E
Stroynowski
I
I
Van Kaer
L
L
Schust
D J
DJ
Ploegh
H
H
Janeway
C A
CA
Scitto
E
E
D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology; D001613:beta 2-Microglobulin / Q000235:genetics / Q000276:immunology
D006183:H-2 Antigens; C024755:H-2K(K) antigen; C032876:H-2Kb protein, mouse; D015395:Histocompatibility Antigens Class I; C032907:Q surface antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D001613:beta 2-Microglobulin