BIO 343 Lecture 5: Chapter 5 Notes
Immunology Chapter 5: Antigen Recognition by T Lymphocytes
Hayden Casassa
• The T cell receptor resembles a membrane associated Fab fragment of immunoglobulin
o TCR’s are alas erae oud
o Made up of alpha chain and beta chain
o 4 Ig domains and transmembrane region
o TCR A and B chain V domains have 3 Ag Binding CDR loops
o One Antigen binding site whih is differet tha BCR’s 2
o TCR recognizes both an antigenic peptide and a Major Histocompatibility Complex (MHC)
molecule present on the surface of another cell
• TCR is specific for both the antigenic peptide and the surrounding surface of the MHC molecule
• Each MHC peptide complex forms a unique ligand for a TCR
o This is eause TCR does’t atuall reogize that peptide ad MHC are differet
• Germline organization is similar to Ab genes (TCR Diversity)
o VDJ gene segments rearrange during T cell development in the Thymus
o Alpha chain only has VJ and C similar to the light chain
o Beta Chain has VDJ and C segment similar to the heavy chain
• Mechanisms that generate TCR diversity are identical to those by B cells
o Gene rearrangement, Junctional Diversity, RAG-1/2, and 12/23 rule
o However, major difference is T cells don’t have somatic hypermutation
▪ Therefore, TCR specificity remains the same after Ag stimulation
▪ TCR repitoire is more diverse ~(1018)
• Organization and arrangement of TCR genes
o Far fewer C gene segments in TCR genes then Ab genes
o Only 1 somatic recombination event for A chain and 2 for B chain
• Severe Combined Immunodeficiency Syndrome (SCID)
o Genetic defect that results in individuals not having functional B or T cells
o One cause is deficiency in RAG proteins which prevent recombination from occurring so B/T
cells die during development
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o “oe people o’t ee ake B/T ells hile others ill ut the just ill ot e futioal
• Omenn Syndrome
o Atypical form of SCID caused by Missense mutation in RAG genes that cause partial loss of RAG
function
▪ Characterized surprisingly by elevated IgE levels (however its abnormal)
▪ Virtual absence of B cells but presence of elevated number of impaired T cells
• Expression and function of the TCR on the cell surface requires association with other proteins and
together form the TCR complex
o Requires 4 invariant proteins
o Three are homologous proteins called CD3 complex- CD3, CD3, and CD3
▪ CD3 is used tie as it sadihes ople o either side
▪ Delta chain is next to Alpha and Beta is with Gamma (Gamma Beta)
o 4th protein is called the chain
o CD3 and the homodimer is required for signal transduction
▪ i.e T cell activation after Ag recognition
o Without all these proteins, and hais do’t een leave the ER where they are made
• Most T ells hae A ad B hais… ut soe hae and chains
o Predominate in gut but are only 1-5% of T cells in circulation
o They bind to various antigenic chemicals directly but do not recognize peptides bound to MHC
molecules
▪ Therefore they are not MHC restricted (in their ability to bind to chemical
• Antigen Processing→ Process where protein antigens are broken down into antigenic peptides inside
the cell
• Antigen Presentation→ Process where peptide antigens are bound by MHC and sent to cell surface
o TCR’s only recognize peptide antigens bound to MHC molecules
o Any cell that presents antigens like this is called an Antigen Presenting Cell (APC)
• Two classes of MHC molecules present peptide to two types of T cells
o MHC Class 1: Present peptide Ags derived from intracellular organisms whose proteins were
degraded in the cytosol
▪ They present antigen to Cytotoxic T cells
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o MHC Class 2: Presents peptide Ags derived from extracellular organisms that were taken up by
cells via phagocytosis and peptides degraded from lysosomes
▪ They present antigen to Helper T cell
o Thik of it like this… Class ou’re like it is too late eause ou’re alread ifeted so ou eed
the cytotoxic T cell to kill ou… Class , ou pik up soethig floatig aroud ut ou ourself
are not infected so you recruit other things (Helper T Cells) to stimulate the immune response
somewhere else
• Cellular Expression of MHC molecules
o MHC Class 1 molecules
▪ All cells express eept RBC’s
▪ Allows all virally-infected to be killed by CD8 T cells
o MHC Class 2 molecules
▪ Professional Antigen Presenting cells
• B cells, macrophages, and dendritic cells
• MHC expression can be upregulated by IFN-
▪ Non-hematopoietic cells (important in T cell development)
• Cytotoxic T cells and CD8 co-receptors
o Cytotoxic T cells express CD8 (CDAte)
o Kills cells infected by intracellular pathogens
o Recognizes peptide antigen presented by MHC Class 1
o CD8 recognizes different part of Class 1 then the TCR
• Helper T cells and CD4 co-receptors
o Helper T cells express CD4 and recognize antigens presented by MHC class 2 molecules
o CD4 recognizes a different part of MHC Class 2 then does the TCR
o Two main types of helper T cells
▪ TH1 cells→ secrete cytokines that activate macrophages so they are better able to kill
pathogens
▪ TFH cells→ secrete cytokines that stimulate B cells to make Abs
• Whe B ell i od sees atige it does’t udergo loal epasio right there
o It needs cytokines in addition from T cell to stimulate B cell to undergo expansion
o Helper T ell’s futio is to release those tokies
o Major cytokine for Macrophage is IFN-y
▪ Structure of MHC Molecules→Both are transmembrane proteins
o MHC Class 1: One chain complexed with smaller 2-microglobulin does’t ar
o MHC Class 2 One chain and one chain
▪ Promiscuous Binding Specificity→ MHC’s a id to ariet of differet atigei peptides
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find more resources at oneclass.com
Document Summary
Immunology chapter 5: antigen recognition by t lymphocytes. If (cid:455)ou are(cid:374)"t i(cid:374)fe(cid:272)ted the(cid:374) all mhc o(cid:374) surfa(cid:272)e ha(cid:448)e hcp peptides. Infections and diseases can modify mhc class 1 pathway. If no invariant chain, mhc class 2 is degraded in the er: summary and comparing peptides and mechanisms. Important class 1 isotypes hla-a, hla-b, and hla-c. The red hla-c molecule could be one of the 1595 possibilities and the dark green one could be another one of the 1595. However, it is possible they are the same and is more likely in the less polymorphic locuses (less allotypes). Immunoproteasome and er chaperone proteins are encoded here too: variation between mhc allotypes (polymorphism) is concentrated in the sites that bind peptides and. Clearl(cid:455) first o(cid:374)e (cid:449)orks ho(cid:449)e(cid:448)er if the mhc (cid:373)ole(cid:272)ule is(cid:374)"t (cid:449)hats (cid:374)eeded or the peptide is(cid:374)"t the e(cid:454)a(cid:272)t o(cid:374)e, the(cid:374) the tcr (cid:272)a(cid:374)"t (cid:271)e activated.
