Major Histocompatibility Complex Molecules MHC Dr morteza Hosseinzadeh
Major Histocompatibility Complex Molecules (( MHC )) Dr : morteza Hosseinzadeh Ilam University of Medical Sciences
Properties of Antigens Recognized By T Lymphocytes q Slight Naïve specific T Cell for one Ag (1 *105 -106 ) q Difference between B & T Cells in Ag Recognition q APC q Most T lymphocytes recognize only short peptides q The antigen receptors of Th & TC cells are specific for peptide antigens that are displayed by MHC molecules
Antigen Capture and The Functions Of Antigen-presenting Cells Ag entrance …………. presented by non-lymphoid cells A ntigen P resenting C ells Ag entrance…………. response by lymphocytes q Different cell types function as APCs to activate naïve T cells or previously differentiated effector T cells q APCs display peptide-MHC complexes for recognition by T cells and also provide additional stimuli that are required for the full responses of the T cells…(Co-ST. molecule, . . CK, …) q The antigen-presenting function of APCs is enhanced by exposure to microbial products…( TLRs, CCR, Adju. , sensors, …) q APCs that present antigens to T cells also receive signals from these lymphocytes that enhance their antigen presenting function…( CD 40 L, IFN-γ… positive feedback…)
Antigen Capture and The Functions Of Antigen-presenting Cells
Antigen Capture and The Functions Of Antigen-presenting Cells
The Major Histocompatibility Complex (MHC) q Self non-self Discrimination q The Human MHC (HLA) q Discovery of the MHC q m. HC (minor H C) Skin Syngeneic And Allograft Transplantation q q ü The Mouse MHC (H-2 Complex): Ch-17 Immune Response Genes… responder / non-responder Alloantibodies against WBC surface proteins : (HLA) The Phenomenon of MHC Restriction… S Transfusion ü KAR ü Multi parturition
The Phenomenon of MHC Restriction Zinkernagel and Doherty
The Major Histocompatibility Complex (MHC) q MHC : q Gene: Human: HLA q Gene Complex: mouse: H 2 q Allele: Dog: q Locus: DLA Rabbit: RLA q Haplotype: Rat: RT-1 q Allogeneic: Hen: B q Polymorphism: Guiney pig: GPLA q homozygote: q Heterozygote:
General Features of MHC genes q The MHC locus contains two types of polymorphic MHC genes, q MHC-I…. endogenous Ag… Tc-CD 8+(CTL)… (B , C , A ) q MHC-II…Exogenous Ag… Th-CD 4+…(DP, DQ, DR ) q non-polymorphic genes whose products are involved in Ag Pres. q Class I and class II MHC genes are the most polymorphic genes present in any mammalian genome. All (10000) / B=3000 q MHC genes are codominantly expressed in each individual.
The Major Histocompatibility Complex (MHC) 2
General Features of MHC genes
General Features of MHC genes Ch: 6 , 3500 Kb , 4 C morgen
General Features of MHC genes pseudo gene class I–like molecules NK cell activity Embryo survival
General Features of MHC genes B 3 B 4 B 5 q HLA-DM …. DMA & DMB non polymorph, similar with MHC-II , facilitate attachment peptide to MHC-II q TAP 1 & TAP 2; ……… peptide transfer to ER q Proteasome: (LMP 2 & LMP 7) …protein lysis and pep. synthesis q HLA-DOA & DOB : ? ? ? In vitro presentation
General Features of MHC genes
General Features of MHC genes
HLA Antigens
General Properties of MHC Molecules q 1) 2) 3) 4) Each MHC molecule consists of an: extracellular peptide binding cleft, immunoglobulin (Ig)–like, domains transmembrane domain cytoplasmic domain q The polymorphic amino acid residues of MHC molecules are located in and adjacent to the peptide-binding cleft. q The non-polymorphic Ig-like domains of MHC molecules contain binding sites for the T cell molecules CD 4 and CD 8. q CD 4+ helper T cells recognize class II MHC molecules displaying peptides, whereas CD 8+ T cells recognize class I MHC molecules with bound peptides.
The Major Histocompatibility Complex (MHC)
The Major Histocompatibility Complex (MHC)
Class-I MHC Molecules 11*25*10 A 90 aa Allo antigenic Site 90 aa 8 -11 MHC-I = α chain + β 2µ + peptide 90 aa CD 8 199 aa 12 Kd 25 aa 30 aa 338 aa 44 -47 Kd (Ig)–like domains
Class I MHC Molecules
Class-II MHC Molecules >30 aa 90 aa MHC-II = α chain + β Chain+ peptide 229 aa 32 -34 Kd 90 aa 237 aa 29 -32 Kd 90 aa 25 aa 10 -15 aa Variable CD 4
Class-II MHC Molecules
Features of Class I and Class II MHC Molecules
The Major Histocompatibility Complex (MHC)
The Major Histocompatibility Complex (MHC)
Human Leukocyte Antigen (HLA) q Public ( Common) Ag : BW 4 , BW 6 q Private (Specific) Ag : A 9 , B 5 , … q Splits
private Splits ü HLA-B 45(12) ü HLA-B 44(12)
Human Leukocyte Antigen (HLA) q Cross-reaction : public Ag subscription between private Ags q Cross-reacting group (CREG)
Expression of MHC Molecules q Class I molecules are expressed on virtually all nucleated cells, whereas class II molecules are expressed only on dendritic cells, B lymphocytes, macrophages, and a few other cell types q The expression of MHC molecules is increased by cytokines produced during both innate and adaptive immune responses. q MHC-I………. IFN-I(α , β) – IFN-γ q MHC-II……. . IFN-γ (APC : DC , MФ , B cell , En , ) q The rate of transcription is the major determinant of the level of MHC molecule synthesis and expression on the cell surface
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