Class I MHC Flashcards
role of MHC class 1
alert CD8+ T cells that the cell is infected by displaying foreign peptide/HLA class I on cell surface
MHC class 1 is expressed on
all nucleated cells including APC
Nomenclature and isotypes of MHC-class 1
MHC- any species HLA class 1- human leukocyte antigen H2-mouse H2-k, D, L Human HLA class I region HLA - A, B, C
normal cells express class 1 isotypes
ABC
HLA class 1 in population are
polymorphic, each isotype has several allels in population
HLA class 1 exhibits
co-dominant expression with six different stable heterodimers possible
HLA class 1 expression is enhance in presence of
IFN gamma
Structure of HLA class 1
transmembrane polymorphic polypeptide heavhy chain non covalently associated with smaller non polymorphic chian Beta 2
Beta 2 microglubulin does not
bind peptide it is needed for protein folding
teritary structure of heavy chian provides
a groove into which peptides of about 10 AA’s binds non covalently
antigen processing and presnetiong with HLA class
- antigens-ubitquitin in cytosol degraded by protesome 2. peptide fragments bind to TAP-1,2 3. Peptide fragments transported into endoplasmic reticulum 4. peptide binds to co-assembled HLA-1/Beta2 microglubulin complex 5. Golgi vesicles containing complexes transported to the cell surface 6. Complexes are released from golgi and fuse with cell membrane 7. HLA-class I/ peptide is now displayed on cell surface
expression of HLA class 1 and foreign peptide signals that
the cell is infected.
Cross presentation
process by which exogenous antigens normally processed in phagolysosomes and presented on the cell surface with MHC class II, are presented by MHC class 1 to CD8+ instead
cross presentation occurs primarily in
dendritic cells.
Cross priming
been documented in viral and non viral infections, cross presentation activation of CD8+
Epstein Barr Virus
HHV-4- causative agent of mono, inhibits proteasome activity and remains a latent infection
Cytomegalovirus
HHV-5- in immunocompromised, may cause numerous disorders (encephalitis, pneumonia, hepatitis, retinitis, or blindness), encodes proteins that redirect newly synthesized calss I MHC molecules from the endoplasmic reticulum back into the cytoplasm for proteasome.
Herpes Simplex Virus
HHV-1:2 Produces an immediate early protein that binds to the cytosolic portion of TAP transporter -inhibits TAP mediated translocation of peptides from the cytosol into the ER -remains life long in neurons because they have little MHC1 class molecules.
Beta 2 is encoded on
chromosome 15.
microorganisms in cytoplasm no enclosed in a vacuole are susceptible to
proteolytic action of proteasome by being targed by ubitquitin
MHC class I restriction
CD8+ only recognize cells infected with virus or other pathogen that display antigenic peptide in association with class I MHC molecules on cell surface
Polymorphism and MHC class I
distinguising characterisitic, shows allelic heterogneity wihtin the population.
CD-1 molecules
glycoproteins that present lipid and glycolipid antigens. to T cells
CD1 molecules are structurally similar to
Class 1 MHC because they form a complex with Beta 2
procesing and cell surface presentation of CD-1 antigen complex is similar to
Class II MHC
five members of CD1
group 1 abc, group 2 de
dendritic cells express all
CD1 members
all CD1 proteisn have
a group of hydrophobic amino acids in a hydrophobic pocket which they can interact with hydrophobic molecules
