Florence Faure

Cellular expression and tissue distribution of the human LAG-3-encoded protein, an MHC class II ligand.

The lymphocyte activation gene 3 (LAG-3), expressed in human activated T and natural killer (NK) cells, is closely related to CD4 at the gene and protein levels (Triebel et al. 1990). The characterization of genomic clones encompassing the LAG-3 locus revealed that the position of the introns in the LAG-3 structure is very close to that of CD4 and that both genes include an intron within the first immunoglobulin superfamily (IgSF) domain. In addition, both genes are located on the distal part of the short arm of chromosome 12 (band p13.3 for LAG-3). Regarding the protein, the LAG-3 cDNA encodes a 470 amino acid (aa) membrane molecule with four extracellular IgSF domains. Although the overall aa sequence similarity with CD4 is barely above background level (<20% sequence identity), analysis of this sequence revealed notable patches of identity with stretches of aa sequences found at the corresponding positions in CD4. Furthermore, as in the CD4 structure, there are some internal sequence homologies in the LAG-3 molecule between domains 1 and 3, as well as between domains 2 and 4, suggesting that LAG-3 has evolved like CD4 by gene duplication from a pre-existing two-IgSF domain structure (see Fig. 1). The close relationship between LAG-3 and CD4 has been further strengthened by the demonstration that both share the same ligand, i.e., major histocompatibility complex (MHC) class II molecules (Baixeras et al. 1992). The initial characterization of the LAG-3-encoded protein has been made possible by the generation of two antibodies, 17B4 and 4F4, directed against a 30 aa

In situ T-cell responses in a primary regressive melanoma and subsequent metastases: a comparative analysis.

In an earlier study of the immune response in a patient with a cutaneous primary regressive melanoma, a T‐cell‐receptor diversity analysis demonstrated in situ amplification of certain lymphocytes. Two of them could be cloned and characterized as CD8+ HLA‐class‐I‐restricted CTL with strong selective anti‐tumor activity. Following a disease‐free period of 3 years, the patient developed a gastric metastasis and subsequently (after an additional year) a metastasis in one axillary lymph node. Melanoma cell lines derived from the 2 secondary lesions have been established here. It was found that these metastatic cells have maintained expression of both HLA‐class‐I molecules and the peptidic antigen(s) recognized by the 2 clones amplified at the primary site. However, the corresponding T lymphocytes were either undetectable or poorly represented both in the gastric and in the axillary lesions. These results suggest that substantial alterations in the quality of T‐cell infiltrates occurred during melanoma progression, despite an apparent stability in presentation of tumor‐associated antigen(s) which initially triggered a positive rejection response. Int. J. Cancer 72:241–247, 1997.