Biology Reference
In-Depth Information
synthetic analogs, indicating that the phosphate moiety is a potential substrate
for enzymatic processing ( Belmant et al., 1999a, 2000). It is tempting to hy-
pothesize that this enzymatic processing could happen on the surface of APCs.
Therefore, surface processing and presentation may constitute the paradigm of
gd TCR of phosphoantigens.
Recognition of MHC Class I-Related Molecules, MICA, and MICB by
Intraepithelial Human V d 1 B T Cells
The nature of the antigens that stimulate Vd1 IELs di¨ers entirely from the
phosphoantigens that stimulate peripheral blood Vg9Vd2 T cells. Likewise, the
biological implications of these responses are di¨erent. Intraepithelial intestinal
Vd1 T cells recognize self-antigens that are distant relatives of MHC class I
molecules (MHC class Ib molecules), called MICA and MICB, and function
as stress-induced antigens (Bahram et al., 1994, 1996). The genes for these
proteins are located close to the HLA-B locus and their expression is under
control of promoters that respond to heat shock. MHC class Ib are not antigen-
presenting molecules but instead function as markers of cell stress or trans-
formation (Groh et al., 1998). MICA/B were detected in cultured and freshly
isolated carcinomas and increased frequencies of Vd1 T cells have been re-
ported in epithelial tumors, especially in those positive for MIC antigens (Groh
et al., 1999). In addition, Groh and colleagues (1998) showed that gd T cells
expanded from a human MICA colon carcinoma were able to recognize
human B lymphoma cells transfected with MICA in a TCR-dependent manner
without antigen processing or presentation of peptide ligands. It has been re-
ported recently that recognition of MICA may involve not only gd TCR but
also the activating NKG2D receptor, resembling recognition of MHC class I
by ab TCR and CD8. Recognition of stress-inducible MICA antigens by gd T
cells may constitute an important surveillance mechanism in defense against
tumors and other epithelial injuries.
ROLE OF gd T CELLS IN THE IMMUNE RESPONSE TO
INFECTIOUS PATHOGENS
Large numbers of microorganisms have been implicated in the activation of gd
T cells. In humans, a role for gd T cells has been proposed in infections with the
following pathogens: S. aureus and Streptococci infections (Abo et al., 1990;
Mochizuki et al., 1994; Munk et al., 1990; Rust et al., 1990); Listeria mono-
cytogenes (Guo et al., 1995; Munk et al., 1990); Brucella (Bertotto et al., 1993);
E. coli (Morita et al., 1995); Salmonella (Abo et al., 1990; Hara et al., 1992);
Yersinia (Young et al., 1997); M. tuberculosis (Barnes et al., 1992; Havlir et al.,
1991; Inoue et al., 1991; Ito et al., 1992; Janis et al., 1989; Kabelitz et al., 1991);
Mycobacterium leprae ( Uyemura et al., 1991); Plasmodia ( Behr and Dubois,
Search WWH ::




Custom Search