HLA molecules and T lymphocytes Flashcards
How does the antigen fit into the antibody
- The outer two domains of HLA molecules form these two alpha helices on a beta pleated sheet
- the antigen fragments fits between the alpha helices
Describe the structure of class 1 HLA
- long alpha chain
- consiters of one domain that resembles the constant region - the other domain resemble the variable region of antibodies and T cell receptor
Describe the structure of the class 2 HLA
- two chains
- each have one domain that resembles constant region
- one domain that resemble the variable region
Describe where the antigen is sitting in a HLA molecule
HLA molecules
- these form two alpha helices that rest on a beta pleated sheet
- the antigen fragment that is being presented rests between the alpha helices
Describe how HLA class I molecules present to CD8 T lymphocytes
- endogenous antigen is presented on class I HLA molecules to CD8 T lymphocytes
Describe how HLA class I molecules present to CD8 T lymphocytes
endogneous antigen is presented on class I HLA molecules to CD8 T lymphocytes
C locus is more concerned with
NK cells
What do class II HLA antigens molecules present to
- Exogenous antigen is presented on class II HLA molecules to CD4 T lymphocytes
What is an endogenous antigen and where is it made
made within the antigen presenting cell
What is an exogenous antigen
- antigen is picked up from the outside
define MHC
- major histocompatibility complex
- this is a cluster of genes that encode molecules involved in antigen presentation (and other genes as well)
- every mammal has one in its genome
What are class I loci HLA
- HLA-A
- HLA - B
- HLA - C
What are class 2 loci HLA
- HLA-DP
- HLA - DQ
- HLA - DR
What are class 2 loci
- HLA-DP
- HLA - DQ
- HLA - DR
Where are HLA class I molecules encoded at
- A locus
- B locus
- C locus
- hundreds alleles at A&B loci in population less at C locus
- any individual can have 2 A locus alleles, 2 B locus alleles and 2 C locus alleles - all of these can be expressed on each cell that expresses class I
Where are HLA class II molecules encoded
- DP
- DQ
- DR
- hundreds of alleles in population
- any individual can have 2 DR locus alleles, 2 DQ locus alleles and 2 DP locus alleles = all of these can be expressed on each cell that expresses class II
what is the nomenclature for naming the class I alleles in HLA
- 8 digits in the lcous letter
- first pair of digits defines the cross reactive group - all the alleles that have the same first two digits have similar shapes on the exposed parts and look the same to antibodies, they represent the alleles as they were originally defined by serology
- the second pair of digits represent differences in the amino acid sequence that cannot be detected by antibodies, these are revealed by molecular biology - the polymorphisms may be within the groove where they cannot be detected by antibodies but can effect peptide selection for presentation and therefore function
- the third pair of digits represents silent polymorphisms within the exons where the amino acid sequence is the same but the DNA base sequence differs
- the fourth pair of digits represents polymorphisms in the introns
what is the nomenclature for naming the alleles
- 8 digits in the lcous letter
- first pair of digits defines the cross reactive group - all the alleles that have the same first two digits have similar shapes on the exposed parts and look the same to antibodies, they represent the alleles as they were originally defined by serology
- the second pair of digits represent differences in the amino acid sequence that cannot be detected by antibodies, these are revealed by molecular biology - the polymorphisms may be within the groove where they cannot be detected by antibodies but can effect peptide selection for presentation and therefore function
- the third pair of digits represents silent polymorphisms within the exons where the amino acid sequence is the same but the DNA base sequence differs
- the fourth pair of digits represents polymorphisms in the introns
describe the nomenclature for the alleles of class II HLA
- there is the added complication that both chains are polymorphic
- DPA locus endoces the DP alpha chain and the DPB locus encodes the DP beta chain
- alleles at each of these loci are named with the locus first
- followed by 8 digits with the same significance as in the class I loci above
What cells express both class I and class II
- antigen presenting cells = dendritic cells, monocytes/macrophages, B lymphocytes express both class I and class II
because in class II the alpha and beta chains can be
because in class II the alpha chains and beta chains can be polymorphic there will be a considerable number of different dimers expressed on any one cell
Expression of HLA molecules are …
upregulated by cytokines especially interferons and especially interferon gamma - thus cells which normally express only class I can be induced to express class II in addition
How are T lymphocytes selected in the thymus
To survive selection process T lymphocytes must be positively selected - must be attracted to some of the HLA peptide complexes displayed in the thymus
- they must not be negatively selected - e.g. they must not be too strongly attracted to any HLA peptide complex in the thymus
How does clonal deletion of T lymphocytes happen
- In the thymus if the receptors on a developing T lymphocyte show a passionate interest in any HLA+ peptide beign expressed on the thymic epithelial cells or dendritic cells
- after leaving the thymus if the T lymphocyte recognises an HLA+ peptide being expressed in a dendritic cell but does not get the second signal via CS28 engaging with its CD80 and CD86 this will be because the dendritic cell does not get danger signals via cytokines e.g. IL-1 & TNF or via its innate receptors such as toll lIke receptors
