T cell responses modulated through interaction between CD8alphaalpha and the nonclassical MHC class I molecule, TL.
The thymus leukemia antigen (TL) is a nonclassical class I molecule, expressed abundantly on intestinal epithelial cells. We show that, in contrast to other major histocompatibility complex (MHC) class I molecules that bind CD8alphabeta, TL preferentially binds the homotypic form of CD8alpha (CD8alphaalpha). Thus, TL tetramers react specifically to CD8alphaalpha-expressing cells, including most intestinal intraepithelial lymphocytes. Compared with CD8alphabeta, which recognizes the same MHC as the T cell receptor (TCR) and thus acts as a TCR coreceptor, high-affinity binding of CD8alphaalpha to TL modifies responses mediated by TCR recognition of antigen presented by distinct MHC molecules. These findings define a novel mechanism of lymphocyte regulation through CD8alphaalpha and MHC class I.
Leishman
A J
AJ
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA.
Naidenko
O V
OV
Attinger
A
A
Koning
F
F
Lena
C J
CJ
Xiong
Y
Y
Chang
H C
HC
Reinherz
E
E
Kronenberg
M
M
Cheroutre
H
H
D020816:Amino Acid Motifs; D000818:Animals; D017951:Antigen Presentation; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D020895:Enterocytes / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D017353:Gene Deletion; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013379:Substrate Specificity; D020349:Surface Plasmon Resonance; D014407:Tumor Cells, Cultured
D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D006183:H-2 Antigens; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; C028388:thymus-leukemia antigens