MHC Molecules

Introduction to MHC

The Major Histocompatibility Complex (MHC) is a key component of the immune system that helps distinguish between 'self' and 'non-self'. Understanding its function and structure is crucial for comprehending immune responses, especially in the context of autoimmunity.

  • Objectives of the Study:

    • Understanding MHC in general.

    • Exploring the organization of MHC genes.

    • Identifying the basic structure of Class I and Class II MHC molecules.

    • Examining the tissue distributions of MHC molecules.

    • Understanding the functions of MHC molecules.

    • Investigating the association of MHC molecules with various diseases.

General Overview of MHC

The Major Histocompatibility Complex consists of genes that encode proteins essential for the immune response. The human variation of MHC is known as Human Leukocyte Antigens (HLA).

  • Definitions:

    • Histo: Refers to tissues.

    • Compatibility: Refers to living together harmoniously.

    • Human Leukocyte Antigens: Refers to MHC molecules in humans.

MHC molecules are expressed on almost all nucleated cells and play a crucial role in antigen presentation and recognition by T cells which is vital for defense against infections and is sometimes implicated in cancer and autoimmune diseases.

Organization and Structure of MHC

Genetic Organization of MHC

The MHC is located on chromosome 6p and contains several classes of genes:

  • Class I and Class II Genes: Encode surface proteins critical for initiating immune responses and antigen presentation to T-cells.

  • Class III and IV Genes:

    • Class III: Involves polymorphic serum proteins related to immune functions (e.g., complement proteins).

    • Class IV: Associated with T-Cell leukemia (Thymus Leukemia Antigen).

Classes of MHC Molecules

MHC molecules can be classified into four main classes:

  • Class I MHC molecules

  • Class II MHC molecules

  • Class III MHC molecules

  • Class IV MHC molecules

Structure of MHC Molecules

  • Class I MHC:

    • Composed of a heavy chain and β2-microglobulin.

    • Heavy chain has five main regions and presents peptide fragments to CD8+ T-cells.

    • Transporter associated with antigen processing (TAP) is vital for peptide transport to the cell surface.

  • Class II MHC:

    • Consists of α and β chains forming a heterodimer, primarily located on B cells, macrophages, and activated T cells.

    • MHC Class II binds exogenous peptides after processing in endosomes.

Tissue Distribution of MHC Molecules

  • Class I MHC: Present on all nucleated cells.

  • Class II MHC: Present on antigen-presenting cells (APCs) like B cells, dendritic cells, and macrophages.

Biological Function of MHC

The MHC plays crucial roles in immune response.

  • Facilitates recognition of infected and tumor cells by cytotoxic T lymphocytes (CTLs).

  • Essential for transplantation compatibility.

  • Influences susceptibility to numerous diseases, including autoimmune conditions.

Connection with Autoimmunity

Autoimmune diseases arise when the immune system fails to distinguish between self and non-self entities.

  • More than 40 autoimmune diseases have known MHC associations affecting a significant percentage of the population.

  • Examples:

    • Narcolepsy: Strong association with HLA-DR2.

    • Ankylosing Spondylitis: Associated with HLA-B27.

HLA and Infectious Diseases

Specific HLA types have been associated with susceptibility and resistance to various infectious diseases:

  • AIDS: Associated with HLA B35, B70 susceptibility; HLA B44, DR7 indicate relative resistance.

  • Malaria: HLA B53 associated with resistance to severe forms.

  • Others: Various diseases like leprosy and tuberculosis show HLA gene associations affecting disease susceptibility.

Conclusion

The MHC is a complex and critical component of the immune system, influencing not only pathogen recognition and response but also impacting individual susceptibility to autoimmune and infectious diseases. Understanding MHC's roles and functioning can enhance our grasp of immunology and help develop therapeutic strategies for managing various immune-related conditions.