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p126 (CDw101), a costimulatory molecule preferentially expressed on mucosal T lymphocytes
G J Russell1, C M Parker, A Sood
1Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston 02115, USA.
Insights
Researchers identified a novel protein, p126 (CDw101), on intestinal lymphocytes. This protein plays a key role in T cell activation and mucosal immunity, offering new insights into immune responses.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Intestinal intraepithelial lymphocytes (IELs) have a unique location but their function remains unclear.
- Understanding IEL function is crucial for deciphering mucosal immunity.
Purpose of the Study:
- To identify cell surface proteins involved in IEL localization and function.
- To characterize novel molecules expressed on mucosal lymphocytes.
Main Methods:
- Development of monoclonal antibodies (mAbs) against human mucosal lymphocytes.
- Immunohistochemical screening, biochemical analysis (SDS-PAGE), peptide mapping, and amino acid sequencing.
- Functional assays including T cell proliferation studies.
Main Results:
- A 200-kDa homodimeric polypeptide, p126, was identified on 88-98% of CD3+ mucosal lymphocytes.
- p126 showed structural similarity to CDw101 and is encoded by the V7 gene.
- Anti-p126 mAbs demonstrated costimulatory activity, enhancing T cell proliferation.
Conclusions:
- p126 is identified as CDw101, a protein with restricted expression on mucosal T lymphocytes.
- CDw101 plays a costimulatory role in T cell activation, particularly relevant for mucosal immunity.
- This finding provides a new target for understanding and manipulating intestinal immune responses.
Abstract:
Intestinal mucosal lymphocytes are defined by their anatomic location within the epithelium (intraepithelial lymphocytes), the interstitium between the epithelial basement membrane and the underlying muscularis mucosa (lamina propria lymphocytes), or in organized lymphoid tissues (Peyer's patches). Although intestinal intraepithelial lymphocytes have a distinct localization, their function has not been determined. To define cell surface proteins that are involved in intestinal intraepithelial lymphocyte localization or function, cultured human mucosal lymphocytes were used as immunogens to develop mAbs that react predominantly with this cell population in an immunohistochemical screening assay. Three mAbs were selected that subsequently were found by biochemical analysis to identify a 200-kDa homodimeric polypeptide on 88 to 98% of CD3+ mucosal lymphocytes but only 18 +/- 13% of PBLs. Expression on granulocytes and monocytes was also observed. This polypeptide has been termed p126 based on its SDS-PAGE-determined M(r) under reducing conditions. Cleveland digest maps demonstrated similarity between the p126 and CDw101 polypeptides. Determined amino acid sequence analysis of the purified p126 polypeptide revealed that it is the protein product of the recently identified V7 gene, which has structural similarities to members of the Ig gene superfamily. Two of the anti-p126 mAbs were costimulatory with suboptimal concentrations of anti-CD3 mAb inducing proliferation of cultured intestinal intraepithelial lymphocytes. Thus, we conclude that p126 is CDw101 encoded by a gene that predicts a seven-Ig domain chain-like structure. It has restricted expression predominantly on mucosal T lymphocytes and appears to have a costimulatory function of special relevance for CD28- T cells and for mucosal lymphocytes.