The T cell receptor

Structure of the TCR

Alpha/beta chains -95% of human lymphocytes; beta/gamma - 5%.

The extracellular portion of each chain is composed of 2 domains: V region domain - farthest away from the membrane, C region- is closest to the membrane.

V region has 3 hypervariable regions.

2 types of TCR:

Alpha/beta TCR - 95% recognizes peptide antigens presented by MHC molecules

Delta/gamma - 5% recognizes lipids as well as peptides; does not always recognize MHC and is not MHC restricted.

Which gene segments make up the alpha and gamma chains in the TCR?

V and J

Which gene segments make up the beta and delta chains in the TCR?

V,J,D

Where are TCR genes rearranged?

In thymus

The recombination activating gene (RAG) enzyme

Initiates immunoglobulin gene rearrangements in B cells. It is also essential for T-cell receptor gene rearrangement.

2 types: RAG -1, RAG-2 and their deficiencies lead to AR-SCID (complete abscence of both T and B cells) - autosomal -recessive severe combined immunodeficiency.

Clinical presentation: in infants during the first 2 weeks of life as lymphopenia with recurrent infections (pneumonia, otitis, skin infections with opportunistic organisms).

Treatment: BMT (bone marrow)

Superantigens

Can activate T cells independent of antigen processing and presentation. They bind directly and simultaneously to MHC II molecules and to certain TCRs with particular beta chains. They provide a massive immune response bc of activation of 1-20% of T cells —> can cause the presence of high levels of cytokines —> cytokine storm → low BP → multiorgan failure (Toxic Shock Syndrome).

T-helper cells

T cells that carry CD4. Usually promote the responsiveness of other cells. Interact with MHC II molecules.

T-killers (cytotoxic T lymphocytes)

T cells that carry CD8 and have killing functions, such as inducing apostolic of virally infected cells. Interact with MHC I molecules

Type 1 of immune rsponse

Type 1 responses focus on intracellular pathogens like viruses and mycobacteria using macrophages and T helper 1 cells.

Type 2 immune response

Type 2 responses involve T helpers 2 cells, mast cells, eosinophils, and IgE to expel large multicellular parasites from mucosal surfaces.

Type 3 immune response

Type 3 responses target extracellular bacteria and fungi, primarily utilizing neutrophils and TH 17 cells