Mim - Lecture 7

Front 1

7.1

MHC

Back 1

- cell communicate to the immune system about antigens that they have encountered
- rejection of tissue grafts

Front 2

7.2

human leukocyte antigen (HLA)

Back 2

MHC protein in human

Front 3

7.3

MHC Class II molecules

Back 3

- HLA-DR, HLA-DQ, HLA-DP in humans
- surface of cells of the immune system
- Eg, B lymphocytes, dendritic cells, macrophages, activated T cells (human)
- inducible on some other cell types
- once expressed, cell becomes visible to CD4+ class II-specific T cells

Front 4

7.4

MHC Class I molecules

Back 4

- HLA-A, HLA-B, HLA-C in humans
- surface of essentially all nucleated cells
- Make cells 'visible' to circulating CD8+ class I-specific T lymphocytes

Front 5

7.5

MHC II structure

Back 5

- 2 chain molecules
- alpha and beta chain
- extracellular portion: alpha 1 and alpha 2, beta 1 and beta 2
- antigen binding groove = alpha 1 + beta 1

Front 6

7.6

MHC I structure:

Back 6

- 2 chain molecules
- alpha (heavy) chain + smaller polypeptide, beta 2 microglobulin
- alpha chain is inserted in the cell membrane
- external: alpha 1 (N terminal), alpha 2 and alpha 3
alpha 3 and beta 2m form a platform
- on top = antigen binding groove formed by alpha 1 and alpha 2

Front 7

7.7

MHC I assembly:

Back 7

- assembled in ER
- picks up a peptide (2000 different kinds)
- peptides are derive from normal degradation of cellular proteins or pathogens

Front 8

7.8

MHC II assembly:

Back 8

- assembled in ER
- picks up a peptide (2000 different kinds)
- peptides are derived from normal degradation of cellular proteins or pathogens

Front 9

7.9

MHC II assembly:

Back 9

- associate w/ a 3rd polypeptide chain in the ER, the invariant chain
- chain blocks peptide binding groove and target MHC II to the endocytic pathway
- once in this pathway, invariant chain is removed
- MHC II is free to bind peptides (same kind as in MHC I)
- after stabilized by bound peptide -> MHC II moves to the cell a surface and interacts w/ T lymphocytes

Front 10

7.10

Major Histocompatibility Complex (MHC) Chromosome:

Back 10

6

Front 11

7.11

Fibroblasts:

Back 11

express only MHC I

Front 12

7.12

T Cell Receptor for Antigen

Back 12

- inserted in the T cell surface, never secreted
- 2 polypeptide chains, alpha, beta
- S-S bond
- CD3

Front 13

7.13

Recognition of Antigenic Peptide-MHC Complexes by TCR

Back 13

- self peptides are ignored b/c T cells w/ TCR to self are negatively selected in the thymus

Front 14

7.14

T cell signaling and adhesion molecules

Back 14

- TCR ligand affinity low
- TCR cytoplasmic tails short
- TCR needs help from other molecules
- CD3, CD4, CD8, LFA1 (adhesion molecule)

Front 15

7.15

TCR antigen recognition

Back 15

- variable region N-terminal
- constant region
- approx. 30000 clonally unique TCR/cell

Front 16

7.16

TCR Dual recognition:

Back 16

- TCR that is specific for a particular MHC-peptide complex is specific for both antigen peptide (Ag restricted) and MHC (MHC restricted)