1. T – CELLS PROMOTE B – CELL DIFFERENTIATION
ANTIGEN
CYTOKINES
PLASMA CELL
ISOTYPE SWITCH AND AFFINITY MATURATION OCCURS IN COLLABORATION WITH T – CELLS ONLY
WHAT IS THE STRUCTURE OF THE T – CELL RECEPTOR?

2. a b B and T cell receptors are similar T-SEJT C V C TCR =  + 
mIg H
mIg L
a b C V
TCR
Antigen receptor
TCR
TCR
TCR =  + 
The -chain variable region is assembled from V – D – J gene segments by recombination – analogous with IgH chain
The α-chain variable region is assembled from V – J
gene segments by recombination – like in IgL - chain
T-SEJT C
Single binding site
No somatic mutation

3. -gene rearrangement results in the elimination of the δ gene
LOCATION OF TCR GENES
-chain locus
Chr 7
L1 V1 Ln Vn D1 J C1 D2 J C2
-enhancer
 and δ-chain locus
Chr 14
TCR1 = 
-silencer, enhancer
L1 Vδ1 L2 Vδ2 L3 Vδ3 Dδ1Dδ2Dδ3Jδ1Jδ2Jδ Cδ L4 Vδ4
TCR2 = δ
-gene rearrangement results in the elimination of the δ gene
-chain locus
Chr 7
L1 V1 Ln Vn J1 C J2 C2
Sequence of D genes allows reading in 3 reading frames
No strict 12 – 23 rule for δ-genes (DJ and VD recombination)

4. further functional (no allele exclusion)
The VARIABLE REGIONS OF - AND -CHAINS ARE GENERATED BY SOMATIC RECOMBINATION
Recombination of V and J genes can occur after multiple unsuccessful recombination
T-CELL
Antigen receptor
TCR
not functional
a/b
next funcional V C
further functional (no allele exclusion)
mRNS

5. -CHAIN -chain Diszulfid hidak CDR1 CDR2 CDR3 -chain V C
CDR1 and CDR2 loops are not hypervariable
NO SOMATIC HYPERMUTATION
Variability of CDR3 is the result of joining variability
CDR1 CDR CDR3

6. ESTIMATED VARIABILITY OF IMMUNOGLOBULIN AND T-CELL RECEPTOR GENES
GÉNEK/
KAPCSOLÓDÁS
IMMUNOGLOBULIN H
 / 
VARIABLE (V) 65 70
DIVERZITY (D) 27
D (3 frame)
rare -
JOINING (J) 6
5/4
JOINING + P + N 2 1
V GENE PAIRS
3.4x106
JOINING
~3x107
TOTAL
~1014
T CELL RECEPTOR   52
~70 2
OFTEN - 13 61 1
5.8x106
~2x1011
1018 NO
SOMATIC HYPERMUTATON

7. T – CELLS PROMOTE B – CELL DIFFERENTIATION
ANTIGEN
CYTOKINES
PLASMA CELL
ISOTYPE SWITCH AND AFFINITY MATURATION OCCURS IN COLLABORATION WITH T – CELLS ONLY
HOW T – CELLS RECOGNIZE ANTIGENS?

8. CHARACTERISTICS OF T-CELL ANTIGEN RECOGNITION
The TCR is not able to interact directly with soluble or cell-bound antigen
T-cell activation can be induced by antigen in the presence of acessory cells, only
3. T-cells recognize virus-infected cells
ACCESSORY CELL
NO INTERACTION
ANTIGEN BINDING
T-CELL ACTIVATION
T-CELL
Antigen receptor
B-CELL

9. T-LYMPHOCYTES RECOGNIZE VIRUS-INFECTED CELLS
T-cells do not interact with virus particles
Cytotoxic T-lymphocytes kill
virus-infected cells
VIrus-infected cell
Citotoxic T-cell
virus
Infected cell
Killed virus-infected cell

10. THE EXPERIMENT OF DOHERTY & ZINKERNAGEL 1976
Virus B
+ Y cells T
Virus A
T - CELLS T
Specific for self and virus
MOUSE Y
Virus A
+ Y cells T
MOUSE X
Virus A
+ X cells T
Virus A
+ X cells T
The virus infected cell must derive from the same organism as the T cell M e d i a G r a p h i c s I n t e r n a t i o n a l

11. (No T cells) THE MAJOR HISTOCOMPATIBILITY GENE COMPLEX MHC Mouse Y
Mouse X
Mouse X
Thymus removal
(No T cells)
HISTOCOMPATIBILITY IS DETERMINED BY GENES OF THE MHC
ORGAN REJECTION IS MEDIATED BY T-CELLS

13. Mouse Y and the congenic Mouse X(Y) carry an identical MHC gene locus
CONGENIC MICE SHARE COMMON MHC GENES
Mouse Y
Mouse X (Y)
Mouse Y and the congenic Mouse X(Y) carry an identical MHC gene locus
T-cells recognize products of MHC genes as self or non-self
If any cell of an individual starts to produce foreign (viral or bacterial) or abnormal (tumor associated) proteins, the T-cells recognize these antigen presenting cells as altered self cells and respond against them

14. The immune response to protein antigens is also dependent on MHC genes
THE MAJOR HISTOCOMPATIBILITY GENE COMPLEX AND THE RESPONE TO PROTEIN ANTIGENS
Antigen
Antigen
Mouse Y
Mouse X
NO IMMUNE RESPONSE
IMMUNE RESPONSE
The immune response to protein antigens is also dependent on MHC genes
Protein antigens are taken up from the environment by phagocytic cells and via MHC proteins present for T-lymphocytes

15. TISSUE TRANSPLANTATION IS RESTRICTED BY MHC MOLECULES
VIRUS-INFECTED CELLS ARE RECOGNIZED BY T-LYMPHOCYTES IN MHC-DEPENDENT MANNER
TISSUE TRANSPLANTATION IS RESTRICTED BY MHC MOLECULES
THE IMMUNE RESPONSE TO PROTEIN ANTIGENS IS REGULATED BY INDIVIDUALLY POLYMORPHIC MHC GENES
T-LYMPHOCYTES RECOGNIZE ANTIGEN-DERIVED PROTEIN FRAGMENTS (PEPTIDES) EXPRESSED ON THE SURFACE OF SELF ANTIGEN PRESENTING CELLS

16. ANTIGEN PRESENTING CELLS
Synthesize antigens – endogenous antigens (virus, tumor)
Internalize antigens – exogenous antigens (any protein)
Degrade protein antigens to peptides – processing
Protein – derived peptides are presented by MHC (HLA) membrane proteins – antigen presentation
MHC molecules present both self and non-self protein – derived peptides
MHC class I molecules are expressed in all nucleated cells
MHC class II molecules are expressed by professional antigen presenting cells

17. Y ANTIGEN RECOGNITION BY T-CELLS REQUIRES
PEPTIDE ANTIGENS AND ANTIGEN PRESENTING CELLS
THAT EXPRESS MHC MOLECULES T Y
Cell surface MHC-peptide complex
T-cell response
soluble Ag
Peptide
antigen
Native
membrane Ag
Cell surface
peptides
APC
No T-cell response

18. PROFESSIONAL ANTIGEN PRESENTING CELLS
Express MHC class I and class II proteins in the cell membrane
Express co-stimulatory molecules (CD40, B7)
B cells – specialized for soluble proteins, toxins
ADAPTIVE
Macrophages – extracellular pathogens (bacteria, yeast)
Dendritic cells – viruses, apoptotic cells
INNATE
T-lymphocytes with αβ TCR recognize MHC – peptide complexes expressed on the surface of professional antigen presenting cells (APC)
T-cell recognition requires the physical contact of APC and T cell

19. MHC RESTRICTION OF T-CELL RECOGNITION
A given TCR recognizes a defined MHC – peptide complex
The same peptide presented by another MHC is not recognized by the same TCR
Another peptide bound to the same MHC is not recognized by the same TCR

20. GENERATION OF MHC CONGENIC MICEP
Mouse X
Mouse Y F1 F2
20 times
Mouse X (Y)

21. Immunoreceptor Tyrosine-based Activation Motif
Assembly of TCR and BCR
Antigen
α β
ε δ ε γ
ζ ζ
ITAM
Immunoreceptor Tyrosine-based Activation Motif
AKTIVÁCIÓ