Selection and expansion of CD8alpha/alpha(1) T cell receptor alpha/beta(1) intestinal intraepithelial lymphocytes in the absence of both classical major histocompatibility complex class I and nonclassical CD1 molecules.
Intestinal intraepithelial lymphocytes (IELs) in mice include two main subsets of TCR-alpha/beta(1) cells which differ functionally and ontogenically from each other. One expresses the CD8alpha/alpha homodimer, whereas the other expresses the CD8alpha/beta heterodimer. Although the presence of all CD8(+)TCR-alpha/beta(1) IELs is dependent on beta2-microglobulin molecules, the nature of the major histocompatibility complex (MHC) class I molecules recognized by the CD8alpha/alpha and the CD8alpha/beta(1) subsets has remained elusive. Using mutant mice lacking the expression of both H2-K(b) and H2-D(b), we show that the CD8alpha/beta(1)TCR-alpha/beta(1) subset is dependent on K or D molecules, whereas the CD8alpha/alpha(1)TCR-alpha/beta(1) subset is independent of classical MHC class I molecules. Furthermore, the CD8alpha/alpha(1) cells are conserved in mice lacking expression of CD1, a nonclassical MHC class I-like molecule previously proposed to be a potential ligand for IELs. Using transporter associated with antigen processing (TAP)-deficient mice, this cell population can be further separated into a TAP-dependent and a TAP-independent subset, suggesting either the recognition of two nonclassical MHC-like molecules, only one of which is TAP dependent, or the involvement of a single nonclassical MHC-like molecule that is only partially TAP dependent. These findings demonstrate that CD8alpha/beta(1)TCR-alpha/beta(1) IELs are restricted by H-2K and H-2D molecules, whereas the unusual subset of CD8alpha/alpha(1)TCR-alpha/beta(1) resident IELs recognize nonclassical MHC class I-like molecules that are distinct from CD1.
Park
S H
SH
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Guy-Grand
D
D
Lemonnier
F A
FA
Wang
C R
CR
Bendelac
A
A
Jabri
B
B
D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D017353:Gene Deletion; D018390:Gene Targeting; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000276:immunology*; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*
D018949:Antigens, CD1; D015395:Histocompatibility Antigens Class I; D016693:Receptors, Antigen, T-Cell, alpha-beta