Immunology Chapter 11 Richard L. Myers, Ph.D. Department of Biology Southwest Missouri State Temple Hall 227 Telephone: 417-836-5307 Email: [email protected].

ImmunologyChapter 11

• Richard L. Myers, Ph.D.

• Department of Biology

• Southwest Missouri State

• Temple Hall 227

• Telephone: 417-836-5307

• Email: [email protected]

T cell receptor

• Nature of the T cell receptor (TCR) recently discovered

• T cell receptor is a cell-surface molecule

• TCR is not specific for antigen alone, but rather antigen in association with an MHC

• TCR studied with monoclonal antibodies and nucleic acid probes

Functional assays for TCR

• TH cells can be assayed by

– proliferation of TH cells

– secretion of various cytokines

– ability to activate TC or B cells

• TC cells can be assayed by

– lysis of target cells– secretion of cytokines

Structure of T cell receptor

• Experimental approaches assumed that there should be a significant difference in the TCR from clone to clone

• Kappler and Marrack – used clonotypic monoclonal antibodies– identified and isolated the TCR

• These researchers and others showed the molecule is composed of an and chain

• TCR is a heterodimer• Contains and chains• Constant and variable

regions• Identified and chains

– 2 - 5% of all T cells

• Very similar to antibody• Variation in amino

terminal end

Organization and rearrangement of TCR genes

• The and TCRs are expressed only in T cells

• The genes for these are very similar to the multigene organization of the Ig genes

• Separate V, D, and J gene segments rearrange during T cell maturation

• Genes composed of introns and exons

• Rearrangements produce more antigenic specificities than antibodies

T cell receptor complex• The TCR associates with CD3

– forms a TCR-CD3 membrane complex

• The CD3 (accessory molecule) is involved in signal transduction after seeing antigen

• CD3 is a complex of 5 invariant chains that form heterodimers– gamma and epsilon chains ()– delta and epsilon chains ()– two zeta chains ()– zeta and eta chains ()

• TCR heterodimer determines binding specificity

• The CD3 dimers are required for– expression of the

TCR

– signal transduction

• The and are members of Ig superfamily

• Both and are different

T cell accessory membrane molecules

• Recognition of an antigen-MHC complex is mediated by the TCR-CD3 complex

• A variety of accessory membrane molecules play a role in recognition and activation– many are adhesion molecules– strengthen the interaction between the two cells– transduce signals through the membrane– some are members of the Ig superfamily

• T cells possess several molecules– CD2

– LFA

– others

• These bind to ligands on APCs or target cells

• Strengthen the association between these cells

CD4 and CD8 coreceptors

• Both CD4 and CD8 play an dual function– adhesion molecules– co-signaling receptors

• CD4+ T cells recognize antigen with class II MHC molecules

• CD8+ T cells recognize antigen with class I MCH molecules

• CD4 is a 55 kDa monomeric membrane glycoprotein– has 4 extracellular domains

• CD8 is a disulfide-linked heterodimer– both are small glycoproteins of approximately

30 - 38 kDa

• CD4 binds to the 2 domain of class II

• CD8 binds to the of a class I

• They react with the same MHC molecule that reacts with the TCR

Assignment

• Read Chapter 12, T-Cell Maturation, Activation and Differentiation

• Review question 1 (pg 309)