HLA molecules and T lymphocytes

Question 1

How does the antigen fit into the antibody

Answer 1

• 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

Question 2

Describe the structure of class 1 HLA

Answer 2

• 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

Question 3

Describe the structure of the class 2 HLA

Answer 3

• two chains
• each have one domain that resembles constant region
• one domain that resemble the variable region

Question 4

Describe where the antigen is sitting in a HLA molecule

Answer 4

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

Question 5

Describe how HLA class I molecules present to CD8 T lymphocytes

Answer 5

• endogenous antigen is presented on class I HLA molecules to CD8 T lymphocytes

Question 6

Describe how HLA class I molecules present to CD8 T lymphocytes

Answer 6

endogneous antigen is presented on class I HLA molecules to CD8 T lymphocytes

Question 7

C locus is more concerned with

Answer 7

NK cells

Question 8

What do class II HLA antigens molecules present to

Answer 8

• Exogenous antigen is presented on class II HLA molecules to CD4 T lymphocytes

Question 9

What is an endogenous antigen and where is it made

Answer 9

made within the antigen presenting cell

Question 10

What is an exogenous antigen

Answer 10

• antigen is picked up from the outside

Question 11

define MHC

Answer 11

• 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

Question 12

What are class I loci HLA

Answer 12

• HLA-A
• HLA - B
• HLA - C

Question 13

What are class 2 loci HLA

Answer 13

• HLA-DP
• HLA - DQ
• HLA - DR

Question 14

What are class 2 loci

Answer 14

• HLA-DP
• HLA - DQ
• HLA - DR

Question 15

Where are HLA class I molecules encoded at

Answer 15

• 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

Question 16

Where are HLA class II molecules encoded

Answer 16

• 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

Question 17

what is the nomenclature for naming the class I alleles in HLA

Answer 17

• 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

Question 18

what is the nomenclature for naming the alleles

Answer 18

• 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

Question 19

describe the nomenclature for the alleles of class II HLA

Answer 19

• 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

Question 20

What cells express both class I and class II

Answer 20

• antigen presenting cells = dendritic cells, monocytes/macrophages, B lymphocytes express both class I and class II

Question 21

because in class II the alpha and beta chains can be

Answer 21

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

Question 22

Expression of HLA molecules are …

Answer 22

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

Question 23

How are T lymphocytes selected in the thymus

Answer 23

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

Question 24

How does clonal deletion of T lymphocytes happen

Answer 24

• 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