Untitled Quiz

Major Histocompatibility Complex (MHC) in Antigen Presentation

• The MHC is a cell surface protein complex that binds to and presents antigenic peptides to T cells.
• MHC genes code for Human Leukocyte Antigens (HLA) proteins.
• Class I and Class II MHC molecules differ in their structure and function, impacting various immunological processes.

Objectives

• Identify MHC genes that code for HLA Class I and Class II molecules.
• Compare and contrast the structure of HLA Class I and Class II molecules.
• Compare and contrast the function of HLA Class I and Class II molecules.
• Compare and contrast HLA Class I and Class II antigen processing and presentation.
• Compare how HLA Class I and Class II genes are expressed on different cell types.
• Understand the role of HLA polymorphism in disease susceptibility and transplant rejection.

The Big Picture of Immune Response

• The immune response involves various cell types including NK, CD4+, and CD8+ T cells and B cells.
• These cells interact through complex mechanisms to eliminate pathogens and maintain immune homeostasis.

The MHC's Role in Antigen Presentation

• Proteins are broken down into peptides by the proteasome within the antigen-presenting cell (APC).
• The peptides then associate with MHC molecules.
• The MHC-peptide complex is displayed on the cell surface.
• T cells recognize this complex and initiate an immune response.

Brief History of MHC Discovery

• MHC was initially discovered in the 1930-1940s in inbred mice via transplantation studies.
• MHC compatibility is crucial for successful transplants and is also crucial for avoiding transplant rejection.
• MHC gene sets are called HLA in humans and H-2 in mice.

MHC: Organization and Classes I, II and III

• MHC proteins are organized into three main classes (Class I, II, and III).
• Class I MHC complex comprises α and ẞ2-microglobulin chain.
• Class II MHC complex comprises α and β chains.
• Class III genes have genes for proteins that are part of the complement system and cytokines.

MHC Class I Molecules

• Composed of an alpha chain and a beta-2 microglobulin molecules.
• Polymorphism exists mostly within the α1 and α2 domains of the peptide-binding groove.

MHC Class II Molecules

• Composed of both alpha and beta chains.
• Allelic variation occurs primarily within the β1 domain.

Inheritance of MHC Genes

• MHC genes are inherited as a set (haplotype) from each parent.
• This leads to a high diversity of MHC proteins across individuals, which can impact immune responses and disease susceptibility.
• HLA coding for the MHC is highly diverse.

HLA-Haplotypes

• Individuals have a high chance of sharing an identical HLA haplotype with closely related family members,.
• HLA haplotypes have a low chance of shared identity between non-related individuals.

MHC Expression on Different Cell Types

• HLA Class I molecules are present on all nucleated cells.
• HLA Class I and II molecules are expressed on professional antigen-presenting cells (APCs).
• HLA Class II expression can be induced by cytokines on some non-professional antigen-presenting cells.

Antigen- Presenting Cell Types

• An antigen-presenting cell (APC) is any cell type that presents antigens to T cells.
• Different APC types present various antigens and interact in different ways with various cell types and situations including inflammation.

MHC and Disease Susceptibility

• Some MHC alleles are linked to a higher risk for specific diseases, like ankylosing spondylitis.
• Some MHC alleles may also influence vaccine responses, like differing responses to certain viral vaccines.
• The MHC's role includes protection against diseases.

Peptide Binding to MHC

• Peptides that bind to different MHC classes are different.
• Peptides are variable even within a singular MHC class.

MHC Class I Antigen Processing Pathway

• Endogenous antigens (inside the APC) are broken down by proteasomes.
• Peptides are transported to the ER by TAP1/2.
• MHC Class I molecules bind to the peptides.
• The MHC-peptide complex is transported to the membrane for presentation to CD8+ T cells.

MHC Class II Antigen Processing Pathway

• Exogenous antigens (from outside the APC) are internalized and degraded into peptides.
• Invariant chain associates with MHCII.
• CLIP (a part of the invariant chain) prevents premature peptide binding.
• HLA-DM catalyzes the exchange of CLIP for antigenic peptides.
• The MHCII-peptide complex is moved to the cell surface for presentation to CD4+ T cells.

B Cells' Role In Antigen Presentation

• B cells can take up foreign antigens and present them within the MHCII.

Cross-Presentation

• Dendritic cells can present exogenous antigens on MHC Class I.
• This allows them to activate cytotoxic T cells
• This is an important way to manage external pathogens.

T Cell Recognition

• T cells recognize the peptide-MHC complex using their T cell receptor (TCR).
• TCR and the MHC-peptide complex is a trimolecular complex.