CD4 stands for cluster of differentiation 4. In CD nomenclature, a CD number is assigned to a cluster of monoclonal antibodies (mAbs) that recognize the same surface molecule and recognize a certain cellular differentiation pattern. CD4 refers to the group of mAbs that recognize the CD4 cell surface molecule and also refers to the CD4 molecule itself. The CD4 molecule is a glycoprotein with four extracellular domains, a transmembrane portion and a short intracellular tail. CD4 is located on the surface of various immune cells and functions in signal amplification and activation of T cells. CD4 defines the helper T cell type and is a well-known clinical cell surface protein marker for HIV progression. While CD8 positive (CD8+) T cells, also known as cytotoxic T cells, directly attack and kill virus-infected cells, CD4+ T cells prime CD8+ T cells and B cells and are also responsible for cytokine production that drives immune cell recruitment.
CD4
CD4 stands for cluster of differentiation 4. CD4 refers to the group of mAbs that recognize the CD4 cell surface molecule found on the surface of immune cells and also refers to the CD4 molecule itself.
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Thamotharampillai Dileepan
May 3, 2021
Nature Biotechnology
The ability to identify T cells that recognize specific peptide antigens bound to major histocompatibility complex (MHC) molecules has enabled enumeration and molecular characterization of the lymphocytes responsible for cell-mediated immunity. Fluorophore-labeled peptide:MHC class I (p:MHCI) tetramers are well-established reagents for identifying antigen-specific CD8+ T cells by flow cytometry, but efforts to extend the approach to CD4+ T cells have been less successful, perhaps owing to lower binding strength between CD4 and MHC class II (MHCII) molecules. Here we show that p:MHCII tetramers engineered by directed evolution for enhanced CD4 binding outperform conventional tetramers for the detection of cognate T cells. Using the engineered tetramers, we identified about twice as many antigen-specific CD4+ T cells in mice immunized against multiple peptides than when using traditional tetramers. CD4 affinity-enhanced p:MHCII tetramers, therefore, allow direct sampling of antigen-specific CD4+ T cells that cannot be accessed with conventional p:MHCII tetramer technology. These new reagents could provide a deeper understanding of the T cell repertoire. The detection of antigen-specific CD4+ T cells is improved with engineered peptide:MHCII tetramers.
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