Biology of the Human gamma T-Cell Receptor

Framework monoclonal antibodies have identified a population of human lymphocytes that express the T3 glycoprotein but not the T-cell receptor (TCR) alpha- and beta-subunits. Chemical crosslinking experiments reveal that these lymphocytes express novel T3-associated polypeptides, one of which appears to be the product of the T gamma gene. The other polypeptide may represent a fourth TCR subunit, designated T delta.

The T-cell repertoire is elaborated by a still poorly understood process during which precursor cells arising in the bone marrow seed the thymus to provide a starting point for intrathymic differentiation and selection. The products of the process are cells which express antigen receptors composed of either alpha/beta or gamma/delta heterodimers in association with CD3. The finding that the appearance of T-cell antigen receptor gamma- and delta-gene rearrangements and transcripts precedes those of full-length beta- and alpha-transcripts during ontogeny indicates that the process is ordered, a conclusion supported by the fact that the appearance of thymocytes expressing CD3-associated gamma/delta heterodimers precedes the appearance of those bearing alpha/beta heterodimers. The recent demonstrations that within the gamma- and delta-loci there is ordered and sometimes transient rearrangement and expression of specific V delta and V gamma gene segments during ontogeny raised the possibility that qualitative changes in the capacity of the differentiative process to generate components of the T-cell armamentarium might occur. We have produced a monoclonal antibody that detects an epitope of the V gamma 3 gene product, a gene segment expressed only in the early fetal thymus. In this report we demonstrate that cells expressing V gamma 3 are present transiently at the earliest stages of thymocyte development, preceding the appearance of cells bearing other gamma/delta or alpha/beta receptors. In the adult mouse, V gamma 3 expression appears to be limited to Thy-1+ cells in the epidermis. These results suggest a profound programming and staging in elaboration of the components of the T-cell system during the early stages of thymocyte development in the embryo.

Human cluster-of-differentiation 1 (CD1) is a family of cell surface glycoproteins of unknown function expressed on immature thymocytes, epidermal Langerhans cells and a subset of B lymphocytes. Three homologous proteins, CD1a, b and c, have been defined serologically, and the CD1 gene locus on human chromosome 1 contains five potential CD1 genes. Analysis of the predicted amino-acid sequences of CD1 molecules reveals a low but significant level of homology to major histocompatibility complex (MHC) class I and class II molecules, and, like MHC class I molecules, CD1 molecules are associated non-covalently with beta 2-microglobulin. These structural similarities to known antigen-presenting molecules, together with the expression of CD1 on cells capable of antigen presentation, suggest a role for CD1 molecules in antigen recognition by T cells. Here we demonstrate the specific recognition of CD1a by a CD4-CD8- alpha beta T-cell receptor (TCR) expressing cytolytic T lymphocyte (CTL) line and the specific recognition of CD1c by a CD4-CD8- gamma delta TCR CTL line. The interaction of CD1-specific CTLs with CD1+ target cells appeared to involve the CD3-TCR complex, and did not show evidence of MHC restriction. These results suggest that for a subset of T cells, CD1 molecules serve a function analogous to that of MHC class I and II molecules.