MHC-restricted T-cell recognition: the basis of immune surveillance

Article Abstract:

Researchers' understanding of the role of T-cells in the immune system at the cellular level has been greatly advanced by the discovery of major histocompatibility gene complex (MHC) restriction and the role of the thymus in T-cell recognition. The role of MHC in restricting T-cell recognition was first realized in a immune trial on mice carried out in the early 1970s, where it was recognized that T-cells were specific for the virus-type and the MHC-type associated with that virus. The fact that T-cells' ability to recognize foreign antigens was not genetically determined, but was the result of the MHC of the host's thymus during the time of T-cell maturation, was the next big discovery in cellular immunity, leading to the 'altered self' hypothesis. In humans, some viral disease susceptibility is associated with the HLA histocompatibility complex, which is the human form of the MHC. In some cases, errors in T-cell response leads to autoimmune diseases. Faulty T-cell response to non-virulent viral stimulus may explain chronic infections such as non-A viral hepatitis and HIV infection.

Thymus, Thymus gland

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The keys to cell-mediated immunity

Article Abstract:

The role of major histocompatibility complex (MHC) glycoproteins in viral immunity has become the focus of research on cell mediated immunity (CMI) since the 1970s, especially in light of the HIV pandemic. Cedric Mims first demonstrated CMI's role in recovery from viral infections in the early 1970s, sparking a wave of research which tended to focus on either genetic factors controlling CD4+ helper T cells, leading to a better understanding of class II MHC glycoproteins, or on studies of CD8+ T lymphocyte action on class I MHC glycoproteins in graft rejections. Research in other areas led to the development of the single T-cell receptor (TCR) 'altered self' model, which led to a unifying theory of T-cell activity. The hypothesis was proven correct after researchers established a two-chain TCR that was consistent with the 'altered self' model.

Research, Immune system

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The concept of antigen processing and presentation

Article Abstract:

The antigen-presenting cell (APC) system plays a major role in regulating cellular immune response. APCs interact with protein antigens, unfolding and partially fragmenting the the protein. At this point, major histocompatibility complex (MHC) molecules are created in the endoplasmic reticulum, after which these MHC molecules bind peptides from the protein and transfer to the surface. APC stimulation then occurs, producing accessory adhesion and stimulatory molecules. These molecules then interact with T-cells, leading to the activation of these T-cells. This explains how the MHC, by continuously sampling the peptides from the proteins in its environment, is malleable in its ability to meet the cell's immunological needs by influencing T-cell behavior.

Analysis, Antigen-antibody reactions

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