L06 Antigen Processing and Presentation Flashcards
Extracellular Antigens
B cells (and their products-antibodies) recognize extracellular antigens or those found or exposed on the outside of the cell
- Neutralization
-Active Complement
-Enhance Phagocytosis
Not all antigens are __________. Typical virus replication cycle; has both Extracellular and Intracellular Phases
Extracellular
Can antibodies gain access to their intracellular environment?
NO
It is a job of the T-lymphocyte system to recognize intracellular antigens
Ag processing and recognition
In order for T cells to recognize antigens derived from within a host cell the antigen must be processed
Exogenous antigen processing pathway:
- HLA class II molecules are involved
- Activation of CD4+ T helper cells
Endogenous antigen processing pathway:
- HLA class I molecules are involved
- Activation of CD8+ cytotoxic T cells
The major histocompatibility complex and HLA molecules:
Nearly every vertebrate has an MHC that encodes genes responsible for determination of self and non-self or determination of foreignness
- Human MHC class I and II genes encodes human leukocyte antigens (HLA)- class I and HLA class II, respectively
The major histocompatibility complex
Genes for MHC are tightly linked on chromosome 6
There are 6 main loci, what are they?
HLA-A, HLA-B and HLA-C for HLA class I
HLA-DP, HLA-DQ and HLA-DR for HLA class II
Genetic Polymorphism Exists
Each gene has multiple different stable forms or ‘alleles’
Each person possesses two sets of MCH genes
- one on each chromosome 6
- diploid (one chromosome 6 from mom and one chromosome 6 from dad)
-each consist of both class I and class II loci
Inherited “en bloc”
according to Mendelian Genetics
- same six from mom and dad
only 4 different combinations, none are genetically identical to mom and dad
- 1/4 siblings have a perfect genetic match
They (HLA class I and II) belong to the ‘ __ _______ family’
(HLA class I and HLA class II molecule)
Ig supergene family
What do the HLA class I molecule and HLA class II molecule have in common?
-both have variable amino acid sequence in peptide binding groove
-both have binding sites for co-receptor on T cells
- Both transmembrane glycoproteins which activate signaling molecules
HLA Class I molecule (structure, T cell interaction and expression)
Structure - Monomer
beta2 microglobulin
T cell interaction - CD8
Expression - MCH class I (endogenous) - all nucleated cells
HLA Class II molecule (structure, T cell interaction and expression)
Structure - dimer
T cell interaction- CD4
Expression - MHC class II (exogenous) APC (antigen presenting cells)
MHC I
Endogenous
MHC II
Exogenous
What type of cell processes exogenous antigens?
If the cell can express HLA class II, it can process and present intracellular Ag to CD4+ T helper cells
Constitutive Expression on:
- Dendritic cells in the spleen & lymph nodes
-Thymic epithelial cells
-B cells
Inducible expression on other cell types such as
- Macrophages
-Fibroblasts
-Endothelial Cells
if CLIP bound to MHC II irreversibly, what would happen?
No peptides would be present
What type of cells process endogenous Ag?
Essentially all nucleated cells (exception may be neutrophils)
- process can be unregulated