Discovery of a Novel MHC Class I Lineage in Teleost Fish which Shows Unprecedented Levels of Ectodomain Deterioration while Possessing an Impressive Cytoplasmic Tail Motif

A unique new nonclassical MHC class I lineage was found in Teleostei (teleosts, modern bony fish, e.g., zebrafish) and Holostei (a group of primitive bony fish, e.g., spotted gar), which was designated “H” (from “hexa”) for being the sixth lineage discovered in teleosts. A high level of divergence of the teleost sequences explains why the lineage was not recognized previously. The spotted gar H molecule possesses the three MHC class I consensus extracellular domains α1, α2, and α3. However, throughout teleost H molecules, the α3 domain was lost and the α1 domains showed features of deterioration. In fishes of the two closely related teleost orders Characiformes (e.g., Mexican tetra) and Siluriformes (e.g., channel catfish), the H ectodomain deterioration proceeded furthest, with H molecules of some fishes apparently having lost the entire α1 or α2 domain plus additional stretches within the remaining other (α1 or α2) domain. Despite these dramatic ectodomain changes, teleost H sequences possess rather large, unique, well-conserved tyrosine-containing cytoplasmic tail motifs, which suggests an important role in intracellular signaling. To our knowledge, this is the first description of a group of MHC class I molecules in which, judging from the sequence conservation pattern, the cytoplasmic tail is expected to have a more important conserved function than the ectodomain.

Generation and molecular recognition of melanoma-associated antigen-specific human γδ T cells

Antigen recognition by T cells bearing αβ T cell receptors (TCRs) is restricted by major histocompatibility complex (MHC). However, how antigens are recognized by T cells bearing γδ TCRs remains unclear. Although γδ T cells can recognize nonclassical MHC, it is generally thought that recognition of antigens is not MHC restricted. Here, we took advantage of an in vitro system to generate antigen-specific human T cells and show that melanoma-associated antigens, MART-1 and gp100, can be recognized by γδ T cells in an MHC-restricted fashion. Cloning and transferring of MART-1–specific γδ TCRs restored the specific recognition of the initial antigen MHC/peptide reactivity and conferred antigen-specific functional responses. A crystal structure of a MART-1–specific γδ TCR, together with MHC/peptide, revealed distinctive but similar docking properties to those previously reported for αβ TCRs, recognizing MART-1 on HLA-A*0201. Our work shows that antigen-specific and MHC-restricted γδ T cells can be generated in vitro and that MART-1–specific γδ T cells can also be found and cloned from the naïve repertoire. These findings reveal that classical MHC-restricted human γδ TCRs exist in the periphery and have the potential to be used in developing of new TCR-based immunotherapeutic approaches.

FUNGSI DAN PEMERIKSAAN LIMFOSIT γδT (Functions and Examination of γδT lymphocytes)

T lymphocytes most have TCR α and β chains. However, TCR formed from γ and δ chains determine a new subset of T lymphocytes. γδTCR specific to different types of ligands, including bacterial phosphoantigen, nonclassical MHC-I molecules and unprocessed protein. γδT lymphocytes have several innate cell-like features that allow their early activation following the recognition of conserved stress-inducedligands. γδ T lymphocytes able to rapidly produce cytokines that regulate pathogen clearance, inflammation and tissue homeostasisin response to tissue stress. They are capable of generating more unique antigen receptors than γδ T lymphocytes and B lymphocytescombined, yet their repertoire of antigen receptors is dominated by specific subsets that recognize a limited number of antigens. A varietyof sometimes conflicting effectors functions have been ascribed to them, yet their biological functions remain unclear. Innate featuresof γδ T lymphocytes underlie their non-redundant role in several physiopathological contexts and are therefore being exploited in thedesign of new immunotherapeutic approaches. The purpose of writing is giving an overview in mainly functions of γδ T lymphocytes inthe immune system and laboratory tests that expand knowledge about the introduction of γδ T lymphocytes.