The Major Histocompatibility Complex (MHC)
Yashmita Shekhawat1*,Vaishali Pareek1 ,Radha Rani Sawami1 ,Anju Kumari1, Nitesh Jat1
1Department of Animal Genetics and Breeding, College of Veterinary and Animal Science, Bikaner, RAJUVAS
*Corresponding author: yashmitashekhawat@gmail.com
The Major Histocompatibility Complex (MHC) constitutes a vital set of surface proteins situated on the cell membrane of nucleated cells. This complex serves a crucial role in distinguishing between self and non-self antigens, facilitating intracellular recognition, and aiding in antigen presentation. The term “Histo” pertains to tissues, while “Compatibility” denotes the harmonious coexistence of living entities. MHC molecules exclusively interact with T lymphocytes, with two main types at play in immunity: MHC II, recognized by T helper cells, and MHC I, recognized by T cytotoxic cells. Further, MHC molecules are categorized into three classes: Class I, Class II, and Class III. These classes delineate the diverse roles and interactions of MHC in the immune system’s intricate processes.
MHC CLASS I
- Class I MHC molecules, with a molecular weight of approximately 45 kD, represent a crucial subset of major histocompatibility antigens. These molecules are ubiquitously expressed on the surface of all nucleated cells except for nervous tissue and platelets. Notably, non-nucleated cells like mammalian red blood cells exhibit minimal to no expression of MHC-I, allowing pathogens within them to evade detection by cytotoxic T cells, as observed in cases such as malaria. Class I MHC molecules function by presenting antigens to T cytotoxic (Tc) cells and binding with CD-8 adhesion molecules on these cells, thereby initiating cell-mediated immune responses. They predominantly facilitate the presentation of intracellular antigens. Noteworthy Class I antigens include HLA-A, HLA-B, and HLA-C, which play a pivotal role in MHC restriction of Cell-Mediated Cytotoxicity, underscoring their significance in immune surveillance and defense mechanisms.
Cytosolic pathway of antigen processing and presentation
- Cytosolic pathway processed and presented the endogenous antigens i.e. those generated within cell eg. Viral infected cells, tumor cells and intracellular pathogens (M. tuberculosis, Histoplasma capsulatum).
- Steps involved in cytosolic pathways are:
- Proteolytic degradation of Ag (protein) into peptides of about 8-10 amino acids.
- These proteins are degraded by cytosolic proteolytic system present in cell called proteasome
- Many proteins targeted for proteolysis have a small protein called ubiquitin attached to them.
- Peptides generated in cytosol by proteasome are transported by TAP (transporter associated with antigen processing) into RER (Rough endoplasmic reticulum)
- Tapasin brings TAP transporter carrying peptides to the proximity with class-I MHC molecule and allows to acquire the antigenic peptides.
- The productive peptide binding with MHC of class-I releases from the complex on the cell surface via golgi complex.
MHC CLASS II
- Class II MHC molecules, characterized by glycoprotein structures, are predominantly expressed on antigen-presenting cells (APCs) including macrophages, dendritic cells, and B-cells. These molecules play a pivotal role in binding peptide antigens and presenting them to CD4 T cells, thereby initiating immune responses. MHC-II molecules are specifically found on the surface of APCs, and their interaction with CD4+ T-cells is integral to activating B cells for antibody production. Notably, exogenous antigens are internalized by professional APCs, where they undergo processing before being presented within the context of MHC-II molecules, highlighting the critical role of MHC-II in the immune recognition and response to extracellular pathogens.
Endocytic pathway of antigen processing and presentation:
- The endocytic pathway processed and present the exogenous Ag. i.e. antigens generated outside the cells. E.g. Bacteria.
- At first APC phagocytosed, endocytosed or both, the antigen.
- Macrophage and dendritic cells internalize the antigen by both the process
- Then antigen is processed and presented on the cell surface along with class-II MHC molecules which are recognized by CD4+TH cell.
MHC CLASS III
- Class III MHC, while initially recognized for encoding secreted proteins with immune functions like those found in the complement system and molecules involved in inflammation, has been further elucidated to encompass a diverse array of genes. Notably, this class contains genes encoding various signaling molecules such as tumor necrosis factors (TNFs) and heat shock proteins. This expanded understanding underscores the multifaceted role of Class III MHC in orchestrating immune responses and regulating cellular processes beyond the traditional scope of antigen presentation and immune recognition.
