USMLE Step 1




B Cells and T Cells



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Major Histocompatibility Complex II (MHC II) is a cell surface protein present only on antigen presenting cells (APCs). It is responsible for presenting exogenous, or externally-derived, antigens to CD4+ Helper T-cells. The structure of MHC II is two chains of similar length, called the alpha and beta chains. These chains are encoded by the HLA- DR, -DQ, and -DP genes, which also encode an invariant chain. Invariant chain is an important placeholder associated with MHC II, which occupies the peptide-binding site prior to delivery to endosomes to prevent binding by endogenous or intracellular antigens. Once MHC II arrives in the acidic environment of the phago-endosome, invariant chain is degraded, allowing externally-derived antigens to bind. MHC II then presents exogenous antigens on the cell surface for CD4+ Helper T cells to inspect.

Key Points

  • Major Histocompatibility Complex II (MHC II)
    • Expressed by Antigen Presenting Cells (APCs)
    • Presents exogenous / externally-derived antigens
      • Usually proteins ingested by phagocytes, e.g. bacterial toxins
      • Antigen loaded in acidic phago-endosome
    • Recognized by CD4+ Helper T-cells
      • Via T-cell receptors (TCRs)
    • Encoded by HLA-DP, -DQ, -DR genes
    • Composed of 2 chains of similar length (alpha and beta)
    • Associated with invariant chain
      • Placeholder occupies antigen-binding site, preventing binding by internal antigens until arrival at endosomes
      • Degraded in the acidified endosome
        • Opens antigen-binding site for externally-derived phagocytized antigens