Future drug developments that may be used for the treatment of autoimmune disease

Question 1

T-cell receptor antagonism - multiple sclerosis

Answer 1

Myelin activated T-cells migrate into the CNS
Encounter further myelin proteins and secrete cytokines
Recruitment of macrophages. which leads to myelin destruction

Question 2

MS susceptibility factors

Answer 2

HLA-DR2
Viral infection

Question 3

T-cell receptor antagonism - peptide based immunotherapy aims

Answer 3

Develop a peptide that can be administered as a drug
Must form a complex with MHC
Must bind to the T-cell receptor without inducing signals that activate the T-cell
Must prevent the native peptide from co-ordinating with the T-cell receptor

Question 4

T-cell receptor antagonism - peptide based immunotherapy example

Answer 4

COP-1, a peptide of 18 amino acids in length, competes with myelin antigens for T-cell receptor binding sites

Question 5

COP-1

Answer 5

Authorised drug (copaxone)
Synthetic peptide compased of aa’s L-ala, L-glu, L-lys, L-tyr
Suppresses experimental models of MS and slow disease progression in humans

Question 6

T-cell receptor antagonism - peptide based immunotherapy - the future

Answer 6

An altered peptide ligand may vary from the native antigen by as little as one amino acids

Question 7

Antagonism of chemokine receptors - rheumatoid arthritis

Answer 7

Activated T-cells and activated macrophages secrete cytokines that activate resident synovial cells to produce proelytic enzymes that mediate tissue damage

Question 8

RA susceptibility factors

Answer 8

H:A-DR1 and 4
Viral infection