Introduction to Immunology

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Introduction to Immunology
Jianzhu Chen Department of Biology Massachusetts
Institute of Technology jchen_at_mit.edu

• Principles of adaptive immunity
• TCR recognition
• Antigen presentation and processing
• Host defense against viruses

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Innate immunity Preformed, non-specific
effectors. Adaptive immunity Immune mechanisms
that are mediated by T and B lymphocytes and that
change in response to infection.
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Principle of the Adaptive Immunity
What is fundamental challenge faced by the immune
system?
Fact
Strategy
Solution
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What are the consequences of using V(D)J
recombination to create antigen receptor
diversity?
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Key molecules and cells of the adaptive immunity
3 molecules 3 cell types 4 cardinal features
Antigen-presenting cells (APC) Dendritic cells
(DC) Macrophage B cells
B cells
T cells
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Antigen recognition by BCR and TCR
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TCR-peptide-MHC (pMHC) interaction
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MHC Structure
Wiley et al. 1987
peptide
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TCR-pMHC interaction
Extensive contacts between TCR and
peptide between TCR and MHC TCR molecules are
evolved to bind to MHC
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TCR-pMHC interaction
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Major Histocompatibility Complex (MHC)
1930s Peter Gorer identified four groups (I, II,
III, and IV) of blood cell antigens in inbred
mice.
1950s George Snell established the group II
antigens mediate rejection of transplanted tumors
and other tissues.
Histocompatibility antigens (H-2 in mouse)
Human Leukocyte Antigens (HLA in human)
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MHC Restriction
MHC type determine the ability of T cell
response.
Zinkernagel Doherty, 1975
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MHC Structure

• Similar to Ig and TCR, belongs to the Ig
  superfamily

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(No Transcript)
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MHC Structure
Peptide-binding proteins Peptide is part of the
stable structure (heterotrimers)
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MHC Structure
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MHC Structure
Class I Class II
Peptide binding domain ?1 / ?2 ?1 / ?1
Peptide binding cleft Closed at both ends Open





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MHC Structure
Class I Class II
Peptide binding domain ?1 / ?2 ?1 / ?1
Peptide binding cleft Closed at both ends Open
Length of peptide 8-10 13-15 (hanging out)




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MHC Structure
Class I Class II
Peptide binding domain ?1 / ?2 ?1 / ?1
Peptide binding cleft Closed at both ends Open
Length of peptide 8-10 13-15 (hanging out)
p-MHC interaction Anchor residues 2 9 No anchor residue



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MHC Structure
Class I Class II
Peptide binding domain ?1 / ?2 ?1 / ?1
Peptide binding cleft Closed at both ends Open
Length of peptide 8-10 13-15 (hanging out)
p-MHC interaction Anchor residues 2 9 No anchor residue



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TCR-pMHC interaction
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MHC Structure
Class I Class II
Peptide binding domain ?1 / ?2 ?1 / ?1
Peptide binding cleft Closed at both ends Open
Length of peptide 8-10 13-15 (hanging out)
p-MHC interaction Anchor residues 2 9 No anchor residue
Source of peptide Cytosolic (endogenous) Endocytic (exogenous)

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MHC Structure
Class I Class II
Peptide binding domain ?1 / ?2 ?1 / ?1
Peptide binding cleft Closed at both ends Open
Length of peptide 8-10 13-15 (hanging out)
p-MHC interaction Anchor residues 2 9 No anchor residue
Source of peptide Cytosolic (endogenous) Endocytic (exogenous)
Expression All nucleated cells Antigen presenting cells (DC, B, MO)

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MHC Structure
Class I Class II
Peptide binding domain ?1 / ?2 ?1 / ?1
Peptide binding cleft Closed at both ends Open
Length of peptide 8-10 13-15 (hanging out)
p-MHC interaction Anchor residues 2 9 No anchor residue
Source of peptide Cytosolic (endogenous) Endocytic (exogenous)
Expression All nucleated cells Antigen presenting cells (DC, B, MO)
T cell recognition CD8 (Cytolytic) CD4 (T helper)
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MHC Nomenclature
Class II
Class I
HLA-DP -DQ -DR
HLA-A -B -C
Human Human Leukocyte Antigen
Example HLA-A2 (or A2), human MHC class I A
molecule, allele 2
Haplotype each set of alleles
H2-Kd (Kd) IAd Balb/c ? H-2d H2-Dd
(Dd) IEd H2-Ld (Ld)
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MHC Function
How can a small number of MHC molecules present a
large number of peptides for TCR recognition?

• Polygenic

Possible MHC class I combinations in one
individual 2A 2B 2C 6
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MHC Function
How can a small number of MHC molecules present a
large number of peptides for TCR recognition?

• Polygenic
• Polymorphic

Presence of multiple alleles at a given locus
within a species
Possible MHC class I combinations in the human
population 470 x 110 x 240 1,240,800
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MHC Function
How can a small number of MHC molecules present a
large number of peptides for TCR recognition?

• Polygenic
• Polymorphic

Extremely polymorphic 5 ? 20 a.a.
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MHC Function
How can a small number of MHC molecules present a
large number of peptides for TCR recognition?

• Polygenic
• Polymorphic
• Co-expression
• Presentation of multiple peptides per MHC
  molecule

gt2,000 peptides per class I molecule gtgt 2,000
peptides per class II molecule 105 molecules per
cell