- T cells require this in order to bind antigen

- do NOT bind free antigen

- must be at the surface of APCs to be seen

MHC (major histocompatibility complex)

- antigens processed/made inside the cell are described as this

- MHC Class I presents this type of antigen to Tc cells

- Usually originate from viruses

Endogenous

- MHC Class II present this type of antigen to Th cells

- primarily from bacterial organisms

- found/made outside the cell

Exogenous

- human MHC

HLA (Human Lymphocyte Antigen)

- this class of genes in the MHC encode glycosylated proteins and are found on nearly all nucleated cells (except red blood cells) and present antigen to Tc cells

- Major region of coding are called A, B, and C

Class I genes

- this class of genes in the MHC codes for glycosylated proteins that are expressed on APCs and present to T Helper cells

- Major regions of coding are DP, DQ, and DR

Class II genes

- this class of genes in the MHC codes for misc proteins

- regions are called C4, C2 and BF

Class III genes

- the MHC genes are closely linked but have many different alleles

- this allows them to be inherited as a group in sets of alleles called this

- you get one of these from each parent

Haplotype

- in contrast to antibody expression, the MHC expresses their alleles in this way

Codominant expression

- in regards to transplants, most individuals are this at different loci which makes it difficult to find an exact match even if it comes from a parent

heterozygous

- this component of the MHC Class I protein is invariant, about 12 kDa, and its gene is not a part of the MHC

- associated with the a3 domain

B2-microglobulin

- this large component of the MHC Class I proteins is transmembranous, about 45 kDa, and has 3 external domains

a chain

- these two domains associate with each other to form the antigen or peptide-binding domain

- form 8 antiparallel B strands and 2 a-helices

- the created groove can hold a peptide of 8-10 aa

a1 & a2

- because the alpha and beta domains of the MHC contain this they belong to the immunoglobulin superfamily

immunoglobulin fold (domains)

- this domain is recognized by the CD8 molecule on T cells

alpha 3

- these three things are required in order for the MHC complex to appear on the surface of the cell

Peptide, a chain, and B2-microglobulin

- Class II molecules have two domains of equivalent size that interact wit this type of bond

Noncovalent

- Class II molecules present to these type of T cells

T helper cells

- the immunoglobulin fold structure is present in a2 and B2 thus making it a member of this

immunoglobulin superfamily

- binding regions for peptide of Class II

a1 and B1

- domain that is recognized by the CD4 molecule from T cells

B2

- Class I MHC carry self-antigens around the body that do not trigger an immune reaction until something changes inside the cell such as this kind of infection

viral infection (viral protein presented)

- in Class I MHC, the antigen must be able to bind to the MHC at the ends of the binding region to allow this to happen to the middle area so TCRs can bind it

- promiscuity of MHC Class I molecules is accomplished because there is variety of the bunched middle region but what in the outer region

Similarity for binding purposes

- the primary difference between the peptide presentation of Class II vs Class I is this

the middle of the peptide doesn't bunch up

(due to extending the peptide out of the binding site)

- it is necessary that all cells are able to present endogenous antigens (Class I) because any of them could have this happen

viral infection

- this marker is added to proteins that need to be broken down

- these marked proteins are directed to proteasomes

Ubiquitin

- NK cells secrete this which causes substitution of two subunits of the proteasome to create an immunoproteasome that helps provide the needed protein fragment for Class I MHC (hydrophobic or basic residue at C terminus)

IFN-y

- this protein is required to transport proteins broken down in immunoproteasomes to the RER

TAP (transporter of antigenic peptides)

- patients with a lack of TAP suffer from this syndrome which makes them highly susceptible to prolonged viral infection

Bare lymphocyte syndrome

- the site of alpha and beta2 microglobulin synthesis in the cell

Polysomes on RER

- molecules that help facilitate the loading of the newly-degraded protein into the MHC Class I groove

calnexin, calreticulin, and tapasin

MHC class I heavy chains bind to this after entering the ER and before binding beta2-microglobulin

calnexin

- the protein that cuts the peptide for the MHC complex down to size

ERAP (endoplasmic reticulum aminopeptidase)

- after being formed in the ER, the MHC complex goes to this organelle and then onto the surface where if activated, the cell will be lysed

Golgi

- after an exogenous antigen is internalized, it is degraded into peptides by this organelle that becomes increasingly acidic

Endosomes

- this chain holds the place of the exogenous antigen until it reaches the endosomes where a Class II antigen is present and ready to take its place

invariant chain ("dummy" place holder)

- because the future MHC Class II complex is in increasingly acidic environments to reach the exogenous antigens the invariant chain is degraded to this

CLIP (Class II-associated invariant chain peptide)

- this facilitates the exchange of CLIP with the exogenous peptide

- class II-like molecule

HLA-DM

- this process helps to propagate a greater immune response to antigens by having crossover of primarily Dendritic cells

Cross-presentation (Class II acting as Class I)

- the enormous diversity found in MHC alleles makes finding a right match for transplantation very difficult

- that problematic diversity is centered in this region of the MHC complex

antigen-binding region