It is well known that lymphocytes with alpha/beta T cell receptors (TCR) recognize short peptides in the context of MHC class I or class II molecules. Thus, lymphocytes with alpha/beta TCR are major histocompatibility complex (MHC)-restricted T cells. However, in the last few decades it has also been well established the notion that T cells can recognize a much broader range of antigens, including carbohydrates, metals, small metabolites and lipids.
T cells can recognize lipid antigens complexed to CD1 molecules. CD1 molecules are very similar to class I MHC antigens. They have an alpha chain associated with beta-2 microglobulin. Alpha chain has a binding groove strongly hydrophobic that specializes in binding different lipids as, for example, phospholipids. In humans, there are 4 isoforms of CD1 able to interact with alpha/beta TCRs: CD1a, CD1b and CD1c (group 1 isoforms) and CD1d isoform, known to interact with invariant NKT cells.
There are different ways in which T cells can respond to CD1 molecules loaded with lipids: first, after the direct interaction with the polar part of the lipid and with the CD1, second after interacting only with the CD1 molecule, and third, after the disruption of the TCR-CD1 binding site by a non-permissive lipid. When an alpha-beta T cell repertoire is being analyzed, it could be important to consider these different kind of interactions with CD1.
These interactions could be relevant in cancer immune response, in autoimmune diseases, allergies or in the response to infections.
Some of these T cells that interact with CD1 loaded with lipids use an invariant alpha chain using only certain V-alpha and J-alpha genes. A strong deviation of V-beta usage has also been detected in certain T cell types.
At Immunerepertoires, in our standard service, we include information about the usage of these V-J combinations and specifically look for data that could point to an expansion of this kind of unconventional T cells.
References:
https://pubmed.ncbi.nlm.nih.gov/33980746/
https://pubmed.ncbi.nlm.nih.gov/36347021/
https://pubmed.ncbi.nlm.nih.gov/35821102/
Picture:
Crystal structure PDB 5WKI