B and T cell antigen receptors are membrane-bound proteins that recognize antigens. B cell receptors (BCRs) are composed of immunoglobulin molecules that recognize intact antigens, while T cell receptors (TCRs) recognize processed antigens presented in the context of MHC class I or II molecules. BCRs are formed through somatic recombination, creating a diverse repertoire. TCRs also undergo genetic recombination of gene segments to generate diversity. Both BCRs and TCRs contain variable regions that determine antigen specificity and transduce activation signals upon antigen binding.

1. B Cell & T Cell Antigen
Specific Receptors

2. B cell Antigen Specific Receptor
• B-cell receptors (BCRs) are
membrane-bound immunoglobulins
that recognize and bind foreign
proteins (antigens).
• BCRs are formed
through random somatic changes
of germline DNA, creating a vast
repertoire of unique sequences
that enable individuals to
recognize a diverse range of
antigens.

3. What are the components of a
BCR receptor?
•Each cell-surface receptor has three main
components:
•An external ligand-binding domain
•A hydrophobic membrane-spanning region
•An intracellular domain inside the cell.

4. What activates the B cell receptor?
• B-cell activation is triggered
by the binding of ligand
(referred to as antigen) to the B-
cell receptor (BCR), which
initiates a cascade of
intracellular signaling leading to
the internalization of antigen for
processing and presentation to T
cells.

5. Where is the B cell receptor (BCR)
Located?
The B cell receptor is
transmembrane protein
composed of a immunoglobulin
molecule and a signal
transduction moiety.

6. What is B cell receptor complex?
• The B-Cell Receptor complex
usually consists of an antigen-
binding subunit (the membrane
immunoglobulin or MIg), which
is composed of two IgHs
(Immunoglobulin Heavy
Chains) and two IgLs
(Immunoglobulin Light
Chains), and a signaling subunit
which is a disulfide-linked
heterodimer of Ig-Alpha
(CD79A) and Ig-Beta (CD79B)

7. What are the differences between B cell
receptors and T cell receptors?
B cell receptor is a transmembrane receptor protein located on the
outer surface of B cells.
T cell receptor is an antigen recognizing molecule present on the
surface of T lymphocytes.
B cell receptor recognizes unprocessed antigens.
T cell receptor recognizes antigens displayed on MHC Class I
and MHC Class II molecules on the surface of antigen
presenting cells/accessary cells.

8. How do B cell receptors
recognize antigens?
•B cells respond to antigens by
engagement of their B-cell antigen
receptor (BCR) and of co-receptors
through which signals from helper T
cells or pathogen-associated molecular
patterns (PAP) are delivered.

9. Do B cells have MHC 1 or 2?
•Besides secreting antibodies, B cells
express MHC class II and serve as
antigen-presenting cells (APCs) for
CD4+ helper T cells.

10. What are antigen Presenting cells?
•Macrophages
•Dendritic cells
•B cells

11. How many binding sites does BCR have?
•Two
•Two heavy (H) chains and two light (L)
chains are held together by inter-chain
disulfide bonds, forming two identical
antigen-binding sites .

12. What is required for B cell activation?
•Naïve B cell activation requires antigen
recognition by the Ig receptor.
• The additional signals that can come
either from a CD4+ Helper T cell
(thymus-dependent)
•Or, in some cases, directly from microbial
components (T independent).

13. How does B cell activation begin?
•B cell activation is initiated by the binding
of antigen to the B cell receptor
(BCR) that triggers a number of signaling
cascades that ultimately lead to B cell
activation.

14. Do B cells bind to MHC?
T cells bind antigens that have been digested
and embedded in MHC molecules by APCs
B cells function as Antigen Presenting Cells
(APC) that bind intact antigens that have
not been processed.

15. How do B cells digest antigens?
•B Cells as Antigen-Presenting Cells
Professional antigen-presenting cells (APCs)
take up antigen through phagocytosis, fluid-
phase pinocytosis, or receptor-mediated
endocytosis for processing, loading of the
digestion products onto MHC Class II (MHC
II) and presentation to CD4 Helper T cells.

16. How many B cell receptors are
there?
•105
•Each B cell has approximately 105 such
receptors in its plasma membrane.
•Each of these receptors is stably associated
with a complex of transmembrane proteins
that activate intracellular signaling pathways
when antigen binds to the receptor.

17. Comparative Structure of BCR
and TCR Receptor Complexes
• BCR complex is composed of
surface immunoglobulin with two
heavy chains and two light chains
along with Ig-Alpha (CD79A) and
Ig-Beta (CD79B)
• TCR complex is composed of one
alpha and one beta chains along
with two units of CD3 molecules

18. T cell Receptor (TCR)
• Principal component TCR was a heterodimeric 90kDa
protein composed of a 40kDa and a 50kDa molecule (α
and β chains)
• Surface molecule on T cells
• Recognize Ag presented in MHC context
• Similar to Immunoglobulin
• Two types of TCR
• α β: predominant in lymphoid tissues
• γ δ: enriched at mucosal surfaces

19. T cell antigen receptor: Some
Fundamentals
One T-cell has one type of TCR
One T-cell has one TCR with a wholly unique
specificity
.
One T-cell has as many as 100,000 identical TCR’s.
There are two important types of T-cells: TH & TC.

20. Structure of the TCR (αβ)
• Regions
–Short cytoplasmic tail- cannot
transduce activation signal
–Transmembrane with
hydrophobic AAs
–Both α and β have a variable
(V) and constant (C) region
–V region is hypervariable,
determines Ag specificity

21. What Cell Receptors do?
Two things:
Respond to MHC
Respond to Ag
More exactly, they see one histotope and many,
many types of processed antigens.

22. TCR

23. Structure of the TCR (αβ)
• Heterodimer
•α and β chains
•approx equal length

24. Important Aspects of TCR
•Each T cell has TCR of only ONE specificity
•Allelic exclusion
•αβ TCR recognizes Ag only in the context of
cell-cell interaction and in correct MHC context
•γδ TCR recognizes Ag in MHC-independent
manner
•Response to certain viral and bacterial Ag

25. Genetic basis for receptor generation
•Accomplished by
recombination of V, D and J
gene segments
•TCR β chain genes have V,
D, and J
•TCR α chain genes have V
and J

26. TCR and CD3 complex
• TCR is closely associated with CD3
complex
• Group of 5 proteins
• Commonly called “invariant” chains of TCR
• Role of CD3 complex
• CD3 necessary for cell surface expression of
TCR
• transduces signal after Ag interaction with
TCR

27. Key steps in T cell activation
•APC must process and present peptides to T cells
•T cells must receive co-stimulatory signal
•Accessory adhesion molecules stabilize binding of
TCR and MHC
•Signal from cell surface is transmitted to nucleus
•Cytokines produced help drive cell proliferation

28. The T cell antigen receptor
Va Vb
Ca Cb
Carbohydrates
Hinge
Monovalent
Resembles an Ig Fab fragment
Fab
VH
VL
Fc
CL
CH
VL
VH
CH CL
CH CH
CH
CH
No alternative constant regions
Transmembrane region
Never secreted
Domain structure: Ig gene superfamily
Heterodimeric, chains are disuphide-
bonded
Cytoplasmic tail
Very short intracytoplasmic tail
+
+
+
Positively charged amino acids in the
TM region
Antigen
combining site
Antigen combining site made of
juxtaposed Va and Vb regions
30,000 identical specificity TcR per cell

29.  T cells
Distinct lineage of cells with unknown functions
1-5% of peripheral blood T cells
In the gut and epidermis of mice, most T cells
express  TcR
Ligands of  TcR are unknown
Possibly recognise:
Antigens without involvement of MHC antigens - CD1
Class IB genes

30. Role of MHC in immune response
•TCR recognizes Ag presented in MHC
•Context is important
•Binding of Ag peptides in non-covalent
•Two types of MHC (class I and class II) are
recognized by different subsets of T cells
•CTL recognizes Ag peptide in MHC class I
•T-helper recognizes Ag peptide in MHC class II

31. Structure of MHC class I
•Two polypeptide chains
•Long α chain and short β

32. Structure of MHC class I
• Four regions
• Cytoplasmic contains sites for
phosphorylation and binding to
cytoskeleton
• Transmembrane contains
hydrophobic AAs
• Highly conserved α3 domain binds
CD8
• Highly polymorphic peptide binding
region formed by α1 and α2

33. Structure of MHC class II
• Two polypeptide chains
• α and β
• approx equal length

34. Structure of MHC class II
• Four regions
• Cytoplasmic contains sites for
phosphorylation and binding
to cytoskeleton
• Transmembrane contains
hydrophobic AAs
• Highly conserved α2 and β2
domains binds CD4
• Highly polymorphic peptide
binding region formed by α1
and β1

35. Important aspects of MHC
• Individuals have a limited number of MHC alleles for each class
• High polymorphism in MHC for a species
• Alleles for MHC genes are co-dominant
• Each MHC gene product is expressed on surface of individual cell

36. Important aspects of MHC
• Each MHC has ONE peptide binding site
• But each MHC can bind many different peptides
• Only one at a time
• Peptide binding is “degenerate”
• MHC polymorphism is determined in germline
• NO recombination mechanisms for creating diversity in
MHC
• Peptide must bind with individual’s MHC to induce
immune response