Magor- Topic 9: CTL Evasion

Question 1

_________ presents peptides from intracellular proteins

Answer 1

MHC class I

Question 2

_________ are linear parts of the intracellular protein that fits right in the cleft of MHC class I

Answer 2

Peptides

Question 3

Viral escape by down-modulating surface expression of MHC: Poliovirus interferes with protein transport in the cell to make vacuoles

Answer 3

• Vesicles budding from ER never make it to the membrane. No new surface proteins get to the cell surface.
• Old MHC, with self peptides bound remain on surface, even though the cell is infected.

Question 4

The ____________ keeps HIV under control for many years

Answer 4

CTL response

Question 5

When ______ declines, opportunistic infections and disease start.

Answer 5

CTL

Question 6

HIV probably initially infects ___________ & ___________ that are in the mucosal tissues where it enters.
Those cells can take up those viruses either by ______________, ____________, or ______________

Answer 6

dendritic cells & macrophages
phagocytosis, presented by MHC class II, or they can also become infected by HIV

Question 7

CTL made in HIV infected individuals are defective.

Answer 7

Even though the cytotoxic T cell response is keeping that virus under control for 2-10 years, we still know that when you actually look at those cytotoxic T cells from an HIV person, about 80% of them are immature. They’re not actually able to kill. They have no ribozymes & perforin that are needed for killing.

Question 8

humans co-dominantly express three _____________ genes

Answer 8

MHC class I (HLA)

one of our genes in our body that we express two alleles

Question 9

An epitope bound by MHC class I is a linear ___ amino acid sequence from within the protein. Viral peptides can be presented if they fit. Each peptide varies except at _______ residues

Answer 9

9
anchor

Question 10

HIV is evolving to eliminate ____________ (especially for common HLA alleles)

Answer 10

CTL epitopes

Question 11

Epitope that you really hope to have is the epitope that

Answer 11

the virus can change

Epitopes that are easy to change

Question 12

Immunodominant epitopes

Answer 12

• CTL immune response tends to focus on a few epitopes originally seen.
• Sometimes called ‘original antigenic sin’
• Focusing first on a really strong epitope & then as that epitope changes it will move to different epitopes.

Question 13

You can take cytotoxic T cells out of a person & just give them ______ in petri culture dish and they will expand & proliferate

Answer 13

IL-2

Question 14

HLA-B27 allele

Answer 14

They noticed that many individuals who are HLA-B27 were fine even though they’ve been infected for years.

Question 15

HLA-B57 allele

Answer 15

• not a common allele
• 11/13 long-term HIV nonprogressors have this allele

Question 16

Nef

Answer 16

• virulence factor
• targets HLA-A and HLA-B for degradation
• HIV makes this
• targets the HLA that’s on the surface
• binds to the cytotoxic tail of HLA & sends it to the endosome for recycling
• binds to the sequences of the proteins for HLA-A & HLA-B, but not HLA-C

Question 17

What happens by having Nef internalizing (remove HLA-A & HLA-B from the surface of the cell but leave HLA-C)?

Answer 17

The cell is no longer a target for cytotoxic T cells & it’s aso not a target for NK cells.

Question 18

Most of the things that the cytotoxic T cell responds are presented by ______ & _______

Answer 18

HLA-A & HLA-B

Question 19

There are many targets of antiretroviral drugs: (3)

Answer 19

• There are inhibitors of the chemokines that prevent entry
• There are protease inhibitors
• There are reverse transcriptase inhibitors

Question 20

HAART- Highly Active Antiretroviral Therapy

Answer 20

By giving these drugs in combination, it suppresses the viral load to the extent that person is no longer considered infectious & works really well.

• AZT
• 3-TC
• Darunavir (binds and blocks active site of the HIV protease

Question 21

Reason why the HIV virus is so challenging

Answer 21

Because of the step where it integrates into the genome of the cells it infects. It makes it basically impossible to get rid of.
It just hangs out there in those infected cells

Question 22

People are trying strategies to get that virus out of the reservoir.

Answer 22

• we don’t really know what the reservoir is, but presumably it’s those CD4 T cells that remain infected.
• could also be some dendritic cells, but most likely CD4 T cell
• some of the strategies attempted are to basically turn on transcription, get that virus making copies of itself & then use antiretroviral therapy to prevent that virus from infecting the next round of cells.

Question 23

Vorinostat

Answer 23

• is a histone deacetylase inhibitor that opens chromatin
• they used this to shock the cells & prevent the virus from thriving

Question 24

ZR59

Answer 24

• pandemic strain

Question 25

Does vaccines prevent HIV infection?

Answer 25

They don’t prevent infection. They prevent disease from that infection

Question 26

what is the best type of HIV vaccine

Answer 26

live attenuated vaccine
- go through a round of replication & presentation to MHC class I

Question 27

These three types of vaccines induce both major histocompatibility complex (MHC) class I and MHC class II antigen presentation and activate pattern recognition receptors (PRRs) expressed by dendritic cells through several pathogen-associated molecular patterns (PAMPs)

Answer 27

Live attenuated, viral vectors and nucleic acid vaccines

Question 28

Killed whole-organism vaccines

Answer 28

activate dendritic cells through the same PAMPs and induce good CD4 and B-cell responses

Question 29

These three vaccines may need an adjuvant for optimal dendritic cell activation and CD4 T-cell priming.

Answer 29

Protein vaccines, viral-like particles, and glycoconjugate vaccines

Question 30

Polysaccharide vaccines

Answer 30

induce a T-cell-independent antibody response